3-10036271-A-G

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.439-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,597,844 control chromosomes in the GnomAD database, including 23,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3423 hom., cov: 29)

Exomes 𝑓: 0.16 ( 20510 hom. )

Consequence

FANCD2
NM_001018115.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.723

Publications

19 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=-0.81).

BP6

Variant 3-10036271-A-G is Benign according to our data. Variant chr3-10036271-A-G is described in ClinVar as Benign. ClinVar VariationId is 257083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCD2	NM_001018115.3 link	c.439-16A>G		intron_variant	Intron 6 of 43	ENST00000675286.1	NP_001018125.1	Q9BXW9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1 link	c.439-16A>G		intron_variant	Intron 6 of 43		NM_001018115.3	ENSP00000502379.1		Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29682

AN:

151020

Hom.:

3419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.0655

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.170

GnomAD2 exomes

AF:

0.162

AC:

40657

AN:

251320

AF XY:

0.161

show subpopulations

Gnomad AFR exome

AF:

0.336

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.0657

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.163

AC:

236401

AN:

1446706

Hom.:

20510

Cov.:

AF XY:

0.163

AC XY:

117783

AN XY:

720572

show subpopulations

African (AFR)

AF:

0.330

AC:

10890

AN:

32988

American (AMR)

AF:

0.158

AC:

7031

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

4053

AN:

26018

East Asian (EAS)

AF:

0.0566

AC:

2244

AN:

39630

South Asian (SAS)

AF:

0.179

AC:

15362

AN:

85934

European-Finnish (FIN)

AF:

0.123

AC:

6564

AN:

53210

Middle Eastern (MID)

AF:

0.163

AC:

930

AN:

5720

European-Non Finnish (NFE)

AF:

0.163

AC:

179478

AN:

1098726

Other (OTH)

AF:

0.165

AC:

9849

AN:

59848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

9318

18636

27954

37272

46590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6422

12844

19266

25688

32110

<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:

0.197

AC:

29707

AN:

151138

Hom.:

3423

Cov.:

AF XY:

0.191

AC XY:

14124

AN XY:

73832

show subpopulations

African (AFR)

AF:

0.320

AC:

13125

AN:

41032

American (AMR)

AF:

0.144

AC:

2189

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

522

AN:

3462

East Asian (EAS)

AF:

0.0654

AC:

338

AN:

5166

South Asian (SAS)

AF:

0.160

AC:

765

AN:

4786

European-Finnish (FIN)

AF:

0.115

AC:

1202

AN:

10438

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10927

AN:

67770

Other (OTH)

AF:

0.170

AC:

358

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

1001

2002

3002

4003

5004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.180

Hom.:

618

Bravo

AF:

0.208

Asia WGS

AF:

0.115

AC:

403

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group D2

Benign:3

Nov 15, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.81

CADD

Benign

0.0080

(source)

DANN

Benign

0.58

PhyloP100

-0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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