Variant 3-10094466-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001018115.3(FANCD2):c.3963+103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 949,642 control chromosomes in the GnomAD database, including 19,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 5960 hom., cov: 32)

Exomes 𝑓: 0.17 ( 13313 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0590

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-10094466-C-T is Benign according to our data. Variant chr3-10094466-C-T is described in ClinVar as [Benign]. Clinvar id is 1235228.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 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.3963+103C>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.3963+103C>T		intron_variant			NM_001018115.3	P2	Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36746

AN:

151852

Hom.:

5953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.464

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.0905

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.205

GnomAD4 exome

AF:

0.171

AC:

136213

AN:

797672

Hom.:

13313

AF XY:

0.171

AC XY:

72467

AN XY:

422938

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.0753

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.242

AC:

36778

AN:

151970

Hom.:

5960

Cov.:

AF XY:

0.236

AC XY:

17559

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.464

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.0903

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.205

Alfa

AF:

0.0793

Hom.:

Bravo

AF:

0.259

Asia WGS

AF:

0.144

AC:

503

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.8

DANN

Benign

0.48

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