rs2272123

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001018115.3(FANCD2):​c.4186-289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 151,856 control chromosomes in the GnomAD database, including 3,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3963 hom., cov: 32)

Consequence

FANCD2
NM_001018115.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.355
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]
FANCD2OS (HGNC:28623): (FANCD2 opposite strand) This gene encodes a conserved protein of unknown function. [provided by RefSeq, Jan 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
Variant 3-10098431-G-A is Benign according to our data. Variant chr3-10098431-G-A is described in ClinVar as [Benign]. Clinvar id is 1270020.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FANCD2NM_001018115.3 linkuse as main transcriptc.4186-289G>A intron_variant ENST00000675286.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FANCD2ENST00000675286.1 linkuse as main transcriptc.4186-289G>A intron_variant NM_001018115.3 P2Q9BXW9-2

Frequencies

GnomAD3 genomes
AF:
0.208
AC:
31492
AN:
151738
Hom.:
3956
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.354
Gnomad AMI
AF:
0.269
Gnomad AMR
AF:
0.153
Gnomad ASJ
AF:
0.151
Gnomad EAS
AF:
0.0650
Gnomad SAS
AF:
0.159
Gnomad FIN
AF:
0.116
Gnomad MID
AF:
0.137
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.179
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.208
AC:
31519
AN:
151856
Hom.:
3963
Cov.:
32
AF XY:
0.202
AC XY:
14981
AN XY:
74232
show subpopulations
Gnomad4 AFR
AF:
0.354
Gnomad4 AMR
AF:
0.153
Gnomad4 ASJ
AF:
0.151
Gnomad4 EAS
AF:
0.0650
Gnomad4 SAS
AF:
0.160
Gnomad4 FIN
AF:
0.116
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.179
Alfa
AF:
0.167
Hom.:
4536
Bravo
AF:
0.219
Asia WGS
AF:
0.115
AC:
402
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxFeb 11, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
1.2
DANN
Benign
0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2272123; hg19: chr3-10140115; API