3-10035158-CTTT-CT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001018115.3(FANCD2):c.378-6_378-5delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,433,924 control chromosomes in the GnomAD database, including 27,271 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4999 hom., cov: 25)

Exomes 𝑓: 0.19 ( 22272 hom. )

Consequence

FANCD2
NM_001018115.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.334

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 was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 3-10035158-CTT-C is Benign according to our data. Variant chr3-10035158-CTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 342255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-10035158-CTT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCD2	NM_001018115.3 link	c.378-6_378-5delTT		splice_region_variant, intron_variant	Intron 5 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.378-14_378-13delTT		intron_variant	Intron 5 of 43		NM_001018115.3	ENSP00000502379.1		Q9BXW9-2

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34235

AN:

149558

Hom.:

4993

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.0663

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.144

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.197

GnomAD2 exomes

AF:

0.233

AC:

42195

AN:

181326

AF XY:

0.230

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.0966

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.190

AC:

243884

AN:

1284262

Hom.:

22272

AF XY:

0.189

AC XY:

121061

AN XY:

639418

show subpopulations

Gnomad4 AFR exome

AF:

0.455

AC:

14309

AN:

31436

Gnomad4 AMR exome

AF:

0.182

AC:

7244

AN:

39796

Gnomad4 ASJ exome

AF:

0.180

AC:

4075

AN:

22646

Gnomad4 EAS exome

AF:

0.0677

AC:

2252

AN:

33286

Gnomad4 SAS exome

AF:

0.202

AC:

15425

AN:

76232

Gnomad4 FIN exome

AF:

0.142

AC:

6434

AN:

45404

Gnomad4 NFE exome

AF:

0.187

AC:

182770

AN:

977580

Gnomad4 Remaining exome

AF:

0.198

AC:

10404

AN:

52638

Heterozygous variant carriers

9327

18653

27980

37306

46633

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

6604

13208

19812

26416

33020

<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:

0.229

AC:

34271

AN:

149662

Hom.:

4999

Cov.:

AF XY:

0.223

AC XY:

16321

AN XY:

73102

show subpopulations

Gnomad4 AFR

AF:

0.422

AC:

0.422437

AN:

0.422437

Gnomad4 AMR

AF:

0.158

AC:

0.157965

AN:

0.157965

Gnomad4 ASJ

AF:

0.152

AC:

0.152453

AN:

0.152453

Gnomad4 EAS

AF:

0.0663

AC:

0.0662627

AN:

0.0662627

Gnomad4 SAS

AF:

0.166

AC:

0.165817

AN:

0.165817

Gnomad4 FIN

AF:

0.123

AC:

0.1228

AN:

0.1228

Gnomad4 NFE

AF:

0.164

AC:

0.164061

AN:

0.164061

Gnomad4 OTH

AF:

0.197

AC:

0.197101

AN:

0.197101

Heterozygous variant carriers

1247

2494

3741

4988

6235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.112

Hom.:

220

Bravo

AF:

0.240

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group D2

Benign:3

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 02, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 15, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:2

Dec 09, 2019

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 17, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

1.0

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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