rs9811771

Positions:

chr3-10092265-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001018115.3(FANCD2):c.3849+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,588,626 control chromosomes in the GnomAD database, including 30,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6451 hom., cov: 30)

Exomes 𝑓: 0.17 ( 24273 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.730

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:

FANCD2OS (HGNC:28623): (FANCD2 opposite strand) This gene encodes a conserved protein of unknown function. [provided by RefSeq, Jan 2013]

FANCD2OS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 3-10092265-A-G is Benign according to our data. Variant chr3-10092265-A-G is described in ClinVar as [Benign]. Clinvar id is 257079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-10092265-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCD2	NM_001018115.3 linkuse as main transcript	c.3849+13A>G		intron_variant		ENST00000675286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCD2	ENST00000675286.1 linkuse as main transcript	c.3849+13A>G		intron_variant			NM_001018115.3	P2	Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37805

AN:

151804

Hom.:

6440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.486

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.0893

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.185

AC:

46335

AN:

251018

Hom.:

5336

AF XY:

0.182

AC XY:

24673

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.0893

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.174

AC:

249645

AN:

1436704

Hom.:

24273

Cov.:

AF XY:

0.174

AC XY:

124831

AN XY:

716414

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.0757

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.249

AC:

37854

AN:

151922

Hom.:

6451

Cov.:

AF XY:

0.243

AC XY:

18064

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.486

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.0891

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.163

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.178

Hom.:

2969

Bravo

AF:

0.266

Asia WGS

AF:

0.158

AC:

550

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group D2

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 11, 2019

- -

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

-0.72

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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