rs6805869

Variant names:

Variant summary

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

The NM_001018115.3(FANCD2):c.2976+36T>C 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 1,369,982 control chromosomes in the GnomAD database, including 23,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5016 hom., cov: 31)

Exomes 𝑓: 0.17 ( 18769 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.354

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=-0.86).

BP6

Variant 3-10078233-T-C is Benign according to our data. Variant chr3-10078233-T-C is described in ClinVar as [Benign]. Clinvar id is 257077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCD2	NM_001018115.3 link	c.2976+36T>C		intron_variant	Intron 30 of 43	ENST00000675286.1	NP_001018125.1	Q9BXW9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1 link	c.2976+36T>C		intron_variant	Intron 30 of 43		NM_001018115.3	ENSP00000502379.1		Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34296

AN:

151858

Hom.:

5011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.0658

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.194

GnomAD3 exomes

AF:

0.169

AC:

42501

AN:

251368

Hom.:

4358

AF XY:

0.167

AC XY:

22621

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.0657

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.168

AC:

204163

AN:

1218006

Hom.:

18769

Cov.:

AF XY:

0.167

AC XY:

103477

AN XY:

618242

show subpopulations

Gnomad4 AFR exome

AF:

0.427

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.0566

Gnomad4 SAS exome

AF:

0.185

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.174

GnomAD4 genome

AF:

0.226

AC:

34330

AN:

151976

Hom.:

5016

Cov.:

AF XY:

0.220

AC XY:

16369

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.0658

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.189

Hom.:

597

Bravo

AF:

0.240

Asia WGS

AF:

0.126

AC:

440

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

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Apr 19, 2022

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.9

DANN

Benign

0.64

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