rs10222446

Variant summary

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

The NM_001018115.3(FANCD2):c.1414-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,117,110 control chromosomes in the GnomAD database, including 48,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 13140 hom., cov: 30)

Exomes 𝑓: 0.28 ( 35531 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.483

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=-0.91).

BP6

Variant 3-10049351-T-C is Benign according to our data. Variant chr3-10049351-T-C is described in ClinVar as [Benign]. Clinvar id is 257068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 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.1414-23T>C		intron_variant		ENST00000675286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCD2	ENST00000675286.1 linkuse as main transcript	c.1414-23T>C		intron_variant			NM_001018115.3	P2	Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

55328

AN:

118078

Hom.:

13119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.414

GnomAD3 exomes

AF:

0.206

AC:

39456

AN:

191370

Hom.:

8907

AF XY:

0.191

AC XY:

19807

AN XY:

103438

show subpopulations

Gnomad AFR exome

AF:

0.759

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.0914

Gnomad SAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.279

AC:

278499

AN:

998934

Hom.:

35531

Cov.:

AF XY:

0.278

AC XY:

138905

AN XY:

499934

show subpopulations

Gnomad4 AFR exome

AF:

0.779

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.222

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.469

AC:

55390

AN:

118176

Hom.:

13140

Cov.:

AF XY:

0.456

AC XY:

26216

AN XY:

57496

show subpopulations

Gnomad4 AFR

AF:

0.774

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.386

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.357

Hom.:

1361

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Fanconi anemia complementation group D2

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 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

-0.91

Cadd

Benign

0.41

Dann

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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