rs3895942

Variant names:

• chr3-10067061-G-C
• rs3895942
• NM_001018115.3:c.2386-148G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-10067061-G-C
• chr3-10067061-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001018115.3(FANCD2):​c.2386-148G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 641,450 control chromosomes in the GnomAD database, including 12,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4901 hom., cov: 32)
  • Exomes 𝑓: 0.16 (7405 hom.)
• Consequence: FANCD2 NM_001018115.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0580
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-10067061-G-C is Benign according to our data. Variant chr3-10067061-G-C is described in ClinVar as Benign. ClinVar VariationId is 1259537.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCD2	NM_001018115.3	c.2386-148G>C		intron_variant	Intron 25 of 43	ENST00000675286.1	NP_001018125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCD2	ENST00000675286.1	c.2386-148G>C		intron_variant	Intron 25 of 43		NM_001018115.3	ENSP00000502379.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34042 AN: 151814 Hom.: 4896 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0655

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.163 AC: 79740 AN: 489518 Hom.: 7405 AF XY: 0.163 AC XY: 43117 AN XY: 263736

African (AFR) AF: 0.410 AC: 5458 AN: 13310

American (AMR) AF: 0.163 AC: 4642 AN: 28456

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 2635 AN: 16912

East Asian (EAS) AF: 0.0549 AC: 1620 AN: 29526

South Asian (SAS) AF: 0.186 AC: 10260 AN: 55304

European-Finnish (FIN) AF: 0.123 AC: 3633 AN: 29452

Middle Eastern (MID) AF: 0.178 AC: 372 AN: 2086

European-Non Finnish (NFE) AF: 0.162 AC: 46532 AN: 287974

Other (OTH) AF: 0.173 AC: 4588 AN: 26498

GnomAD4 genome AF: 0.224 AC: 34075 AN: 151932 Hom.: 4901 Cov.: 32 AF XY: 0.219 AC XY: 16229 AN XY: 74248

African (AFR) AF: 0.413 AC: 17117 AN: 41408

American (AMR) AF: 0.155 AC: 2358 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3472

East Asian (EAS) AF: 0.0655 AC: 339 AN: 5178

South Asian (SAS) AF: 0.166 AC: 801 AN: 4820

European-Finnish (FIN) AF: 0.117 AC: 1230 AN: 10554

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11018 AN: 67938

Other (OTH) AF: 0.193 AC: 407 AN: 2106

Alfa AF: 0.185 Hom.: 391

Bravo AF: 0.238

Asia WGS AF: 0.125 AC: 438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 11, 2019

GeneDx

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	-0.92
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		-0.058
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3895942; hg19: chr3-10108745;