Variant chr3-10065836-G-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.2270-28G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,417,858 control chromosomes in the GnomAD database, including 21,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3260 hom., cov: 32)

Exomes 𝑓: 0.17 ( 18497 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.04

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:

FANCD2 (HGNC:):

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=-0.8).

BP6

Variant 3-10065836-G-T is Benign according to our data. Variant chr3-10065836-G-T is described in ClinVar as [Benign]. Clinvar id is 257074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 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.2270-28G>T		intron_variant		ENST00000675286.1	NP_001018125.1	Q9BXW9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1 linkuse as main transcript	c.2270-28G>T		intron_variant			NM_001018115.3	ENSP00000502379.1		Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29439

AN:

151974

Hom.:

3256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.0641

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.169

GnomAD3 exomes

AF:

0.160

AC:

39693

AN:

247714

Hom.:

3485

AF XY:

0.160

AC XY:

21468

AN XY:

134032

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.0650

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.166

AC:

210428

AN:

1265766

Hom.:

18497

Cov.:

AF XY:

0.166

AC XY:

106263

AN XY:

639718

show subpopulations

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.0565

Gnomad4 SAS exome

AF:

0.184

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.194

AC:

29462

AN:

152092

Hom.:

3260

Cov.:

AF XY:

0.189

AC XY:

14024

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.308

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.0640

Gnomad4 SAS

AF:

0.165

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.175

Hom.:

469

Bravo

AF:

0.203

Asia WGS

AF:

0.113

AC:

396

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 provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 11, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.7

DANN

Benign

0.70

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