chr3-10065836-G-T

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.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

Publications

8 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=-0.8).

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 rank	MANE	Protein	UniProt
FANCD2	NM_001018115.3 link	c.2270-28G>T		intron_variant	Intron 24 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.2270-28G>T		intron_variant	Intron 24 of 43		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

GnomAD2 exomes

AF:

0.160

AC:

39693

AN:

247714

AF XY:

0.160

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 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

African (AFR)

AF:

0.320

AC:

9472

AN:

29620

American (AMR)

AF:

0.157

AC:

6957

AN:

44290

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

3891

AN:

24762

East Asian (EAS)

AF:

0.0565

AC:

2188

AN:

38738

South Asian (SAS)

AF:

0.184

AC:

15128

AN:

82290

European-Finnish (FIN)

AF:

0.123

AC:

6547

AN:

53164

Middle Eastern (MID)

AF:

0.162

AC:

869

AN:

5370

European-Non Finnish (NFE)

AF:

0.168

AC:

156450

AN:

933702

Other (OTH)

AF:

0.166

AC:

8926

AN:

53830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

8581

17162

25742

34323

42904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5256

10512

15768

21024

26280

<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:

0.194

AC:

29462

AN:

152092

Hom.:

3260

Cov.:

AF XY:

0.189

AC XY:

14024

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.308

AC:

12759

AN:

41470

American (AMR)

AF:

0.144

AC:

2197

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

523

AN:

3472

East Asian (EAS)

AF:

0.0640

AC:

331

AN:

5170

South Asian (SAS)

AF:

0.165

AC:

794

AN:

4826

European-Finnish (FIN)

AF:

0.116

AC:

1226

AN:

10578

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

10993

AN:

67988

Other (OTH)

AF:

0.170

AC:

358

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1166

2331

3497

4662

5828

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:

0.179

Hom.:

513

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

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.80

CADD

Benign

6.7

(source)

DANN

Benign

0.70

PhyloP100

1.0

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