3-10067241-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_001018115.3(FANCD2):c.2418T>G(p.Pro806Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,613,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

FANCD2
NM_001018115.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.265

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 3-10067241-T-G is Benign according to our data. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655. Variant chr3-10067241-T-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 414655.

BP7

Synonymous conserved (PhyloP=-0.265 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCD2	NM_001018115.3 link	c.2418T>G	p.Pro806Pro	synonymous_variant	Exon 26 of 44	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.2418T>G	p.Pro806Pro	synonymous_variant	Exon 26 of 44		NM_001018115.3	ENSP00000502379.1		Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000107

AC:

AN:

251256

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000992

AC:

145

AN:

1461056

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

726870

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33458

American (AMR)

AF:

0.000313

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000112

AC:

125

AN:

1111324

Other (OTH)

AF:

0.0000497

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000131

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41442

American (AMR)

AF:

0.000262

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000178

Hom.:

Bravo

AF:

0.000144

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Fanconi anemia complementation group D2

Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Fanconi anemia

Benign:1

Nov 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FANCD2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.7

(source)

DANN

Benign

0.59

PhyloP100

-0.27

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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