rs6785756

Positions:

chr3-10049469-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001018115.3(FANCD2):c.1509C>T(p.Asn503=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 1068 hom., cov: 32)

Exomes 𝑓: 0.045 ( 3032 hom. )

Failed GnomAD Quality Control

Consequence

FANCD2
NM_001018115.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.872

Variant links:

Genes affected

FANCD2 (HGNC:3585): (FA complementation group D2) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group D2. This protein is monoubiquinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins (BRCA1 AND BRCA2) involved in homology-directed DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

FANCD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-10049469-C-T is Benign according to our data. Variant chr3-10049469-C-T is described in ClinVar as [Benign]. Clinvar id is 257070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.872 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCD2	NM_001018115.3 linkuse as main transcript	c.1509C>T	p.Asn503=	synonymous_variant	17/44	ENST00000675286.1	NP_001018125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1 linkuse as main transcript	c.1509C>T	p.Asn503=	synonymous_variant	17/44		NM_001018115.3	ENSP00000502379	P2	Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

21029

AN:

132134

Hom.:

1066

Cov.:

FAILED QC

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.0520

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0896

Gnomad MID

AF:

0.145

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.0300

AC:

7152

AN:

238040

Hom.:

638

AF XY:

0.0284

AC XY:

3669

AN XY:

128990

show subpopulations

Gnomad AFR exome

AF:

0.0915

Gnomad AMR exome

AF:

0.0402

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.0213

Gnomad SAS exome

AF:

0.0371

Gnomad FIN exome

AF:

0.00476

Gnomad NFE exome

AF:

0.0236

Gnomad OTH exome

AF:

0.0372

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0452

AC:

57650

AN:

1275376

Hom.:

3032

Cov.:

AF XY:

0.0473

AC XY:

30103

AN XY:

636740

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.0566

Gnomad4 ASJ exome

AF:

0.0641

Gnomad4 EAS exome

AF:

0.0282

Gnomad4 SAS exome

AF:

0.0929

Gnomad4 FIN exome

AF:

0.0455

Gnomad4 NFE exome

AF:

0.0380

Gnomad4 OTH exome

AF:

0.0594

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.159

AC:

21047

AN:

132256

Hom.:

1068

Cov.:

AF XY:

0.153

AC XY:

9907

AN XY:

64558

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.0519

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.0896

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.127

Hom.:

171

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 12, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia complementation group D2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 23, 2023

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.1

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over