rs6805869

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001018115.3(FANCD2):c.2976+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,369,982 control chromosomes in the GnomAD database, including 23,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5016 hom., cov: 31)

Exomes 𝑓: 0.17 ( 18769 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.354

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

Fanconi anemia complementation group D2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FANCD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 3-10078233-T-C is Benign according to our data. Variant chr3-10078233-T-C is described in ClinVar as Benign. ClinVar VariationId is 257077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCD2	NM_001018115.3 link	c.2976+36T>C		intron_variant	Intron 30 of 43	ENST00000675286.1	NP_001018125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1 link	c.2976+36T>C		intron_variant	Intron 30 of 43		NM_001018115.3	ENSP00000502379.1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34296

AN:

151858

Hom.:

5011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.0658

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.194

GnomAD2 exomes

AF:

0.169

AC:

42501

AN:

251368

AF XY:

0.167

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.0657

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.168

AC:

204163

AN:

1218006

Hom.:

18769

Cov.:

AF XY:

0.167

AC XY:

103477

AN XY:

618242

show subpopulations

African (AFR)

AF:

0.427

AC:

12230

AN:

28610

American (AMR)

AF:

0.162

AC:

7199

AN:

44350

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

3834

AN:

24578

East Asian (EAS)

AF:

0.0566

AC:

2180

AN:

38496

South Asian (SAS)

AF:

0.185

AC:

14998

AN:

81278

European-Finnish (FIN)

AF:

0.123

AC:

6549

AN:

53164

Middle Eastern (MID)

AF:

0.165

AC:

869

AN:

5252

European-Non Finnish (NFE)

AF:

0.165

AC:

147191

AN:

889918

Other (OTH)

AF:

0.174

AC:

9113

AN:

52360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

8426

16852

25277

33703

42129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4862

9724

14586

19448

24310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.226

AC:

34330

AN:

151976

Hom.:

5016

Cov.:

AF XY:

0.220

AC XY:

16369

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.419

AC:

17366

AN:

41400

American (AMR)

AF:

0.156

AC:

2376

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

523

AN:

3472

East Asian (EAS)

AF:

0.0658

AC:

340

AN:

5168

South Asian (SAS)

AF:

0.165

AC:

794

AN:

4814

European-Finnish (FIN)

AF:

0.116

AC:

1226

AN:

10584

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

11015

AN:

67960

Other (OTH)

AF:

0.194

AC:

408

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1226

2452

3679

4905

6131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

667

Bravo

AF:

0.240

Asia WGS

AF:

0.126

AC:

440

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group D2

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Apr 19, 2022

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.9

(source)

DANN

Benign

0.64

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over