Variant 3-10048089-A-C 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.1413+38A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,556,388 control chromosomes in the GnomAD database, including 3,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 217 hom., cov: 47)

Exomes 𝑓: 0.12 ( 2830 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.402

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-10048089-A-C is Benign according to our data. Variant chr3-10048089-A-C is described in ClinVar as [Benign]. Clinvar id is 257067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCD2	NM_001018115.3 linkuse as main transcript	c.1413+38A>C		intron_variant		ENST00000675286.1	NP_001018125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1 linkuse as main transcript	c.1413+38A>C		intron_variant			NM_001018115.3	ENSP00000502379	P2	Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16222

AN:

150984

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.0914

Gnomad ASJ

AF:

0.0891

Gnomad EAS

AF:

0.0430

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0657

Gnomad MID

AF:

0.0769

Gnomad NFE

AF:

0.0884

Gnomad OTH

AF:

0.0952

GnomAD4 exome

AF:

0.119

AC:

166639

AN:

1405282

Hom.:

2830

Cov.:

AF XY:

0.117

AC XY:

82302

AN XY:

700940

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.0999

Gnomad4 EAS exome

AF:

0.0381

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.0705

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.107

AC:

16242

AN:

151106

Hom.:

217

Cov.:

AF XY:

0.104

AC XY:

7713

AN XY:

73868

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.0911

Gnomad4 ASJ

AF:

0.0891

Gnomad4 EAS

AF:

0.0429

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0657

Gnomad4 NFE

AF:

0.0884

Gnomad4 OTH

AF:

0.0951

Alfa

AF:

0.159

Hom.:

845

Bravo

AF:

0.205

Asia WGS

AF:

0.113

AC:

395

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	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.84

CADD

Benign

5.5

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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