rs9809061

Variant summary

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

The NM_001018115.3(FANCD2):c.990-38C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,510,920 control chromosomes in the GnomAD database, including 25,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5025 hom., cov: 32)

Exomes 𝑓: 0.17 ( 20891 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.925

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-10043446-C-G is Benign according to our data. Variant chr3-10043446-C-G is described in ClinVar as [Benign]. Clinvar id is 257088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 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.990-38C>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.990-38C>G		intron_variant			NM_001018115.3	P2	Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34328

AN:

151836

Hom.:

5019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.0654

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.194

GnomAD3 exomes

AF:

0.167

AC:

41368

AN:

247316

Hom.:

4140

AF XY:

0.165

AC XY:

22220

AN XY:

134314

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.0653

Gnomad SAS exome

AF:

0.177

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.168

AC:

228455

AN:

1358966

Hom.:

20891

Cov.:

AF XY:

0.168

AC XY:

114340

AN XY:

682076

show subpopulations

Gnomad4 AFR exome

AF:

0.429

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.0566

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.226

AC:

34364

AN:

151954

Hom.:

5025

Cov.:

AF XY:

0.220

AC XY:

16368

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.0654

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.113

Hom.:

224

Bravo

AF:

0.240

Asia WGS

AF:

0.125

AC:

438

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Genome-Nilou Lab	Aug 10, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.88

Cadd

Benign

3.8

Dann

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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