NM_000135.4(FANCA):c.3934+2T>C AND Fanconi anemia complementation group A

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 4, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000669249.6

Allele description [Variation Report for NM_000135.4(FANCA):c.3934+2T>C]

NM_000135.4(FANCA):c.3934+2T>C

Genes:

FANCA:FA complementation group A [Gene - OMIM - HGNC]
ZNF276:zinc finger protein 276 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000135.4(FANCA):c.3934+2T>C

HGVS:

NC_000016.10:g.89739992A>G
NG_011706.1:g.81666T>C
NM_000135.2:c.[3934+2T>C]
NM_000135.4:c.3934+2T>CMANE SELECT
NM_001113525.2:c.*1746A>GMANE SELECT
NM_001286167.3:c.3934+2T>C
NM_152287.4:c.*1746A>G
LRG_495t1:c.3934+2T>C
LRG_495t1:c.[3934+2T>C]
LRG_495:g.81666T>C
NC_000016.9:g.89806400A>G
NM_000135.2:c.3934+2T>C
NM_000135.2:c.[3934+2T>C]
NM_000135.4:c.3934+2T>C
NR_110122.2:n.3746A>G
NR_110126.2:n.3629A>G
NR_110128.2:n.3569A>G
NR_110129.2:n.3663A>G

Links:

dbSNP: rs771775516

NCBI 1000 Genomes Browser:

rs771775516

Molecular consequence:

NM_001113525.2:c.*1746A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152287.4:c.*1746A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NR_110122.2:n.3746A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110126.2:n.3629A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110128.2:n.3569A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_110129.2:n.3663A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000135.4:c.3934+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001286167.3:c.3934+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Fanconi anemia complementation group A
Synonyms:: Fanconi anemia, group A
Identifiers:: MONDO: MONDO:0009215; MedGen: C3469521; Orphanet: 84; OMIM: 227650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793983	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Sep 6, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002073175	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004196091	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 4, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793983

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Sep 6, 2017)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV002073175

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004196091

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 4, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification and characterization of novel mutations of the major Fanconi anemia gene FANCA in the Japanese population.

Yagasaki H, Hamanoue S, Oda T, Nakahata T, Asano S, Yamashita T.

Hum Mutat. 2004 Dec;24(6):481-90.

PubMed [citation]

PMID:: 15523645

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Counsyl, SCV000793983.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV002073175.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The splice donor variant c.3934+2T>C in FANCA (NM_000135.4) has been reported to ClinVar as Likely Pathogenic. The c.3934+2T>C variant is observed in 1/30,616 (0.0033%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant mutates a splice-donor sequence, potentially resulting in the retention of large segments of intronic DNA by the mRNA and nonfunctional proteins. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004196091.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 17, 2024

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