Variant 3-10064460-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001018115.3(FANCD2):c.2021+31C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 110,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 0 hom., cov: 33)

Exomes 𝑓: 0.082 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.775

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=-0.71).

BP6

Variant 3-10064460-C-T is Benign according to our data. Variant chr3-10064460-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 210979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 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.2021+31C>T		intron_variant		ENST00000675286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCD2	ENST00000675286.1 linkuse as main transcript	c.2021+31C>T		intron_variant			NM_001018115.3	P2	Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

13601

AN:

110536

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0981

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.0756

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.0101

AC:

2204

AN:

217758

Hom.:

AF XY:

0.00907

AC XY:

1082

AN XY:

119264

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.00798

Gnomad ASJ exome

AF:

0.00299

Gnomad EAS exome

AF:

0.0364

Gnomad SAS exome

AF:

0.00999

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.00621

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0823

AC:

69207

AN:

840904

Hom.:

Cov.:

AF XY:

0.0792

AC XY:

33718

AN XY:

425622

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.0321

Gnomad4 ASJ exome

AF:

0.0525

Gnomad4 EAS exome

AF:

0.146

Gnomad4 SAS exome

AF:

0.0656

Gnomad4 FIN exome

AF:

0.0695

Gnomad4 NFE exome

AF:

0.0847

Gnomad4 OTH exome

AF:

0.0864

GnomAD4 genome

AF:

0.123

AC:

13615

AN:

110614

Hom.:

Cov.:

AF XY:

0.123

AC XY:

6683

AN XY:

54198

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.0981

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.0706

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.121

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 01, 2015

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 19, 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

-0.71

CADD

Benign

5.8

DANN

Benign

0.82

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