Variant X-101231660-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BS2_Supporting

The NM_001939.3(DRP2):c.13G>A(p.Val5Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000365 in 1,097,074 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000036 ( 0 hom. 3 hem. )

Consequence

DRP2
NM_001939.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.55

Variant links:

Genes affected

DRP2 (HGNC:3032): (dystrophin related protein 2) Members of the dystrophin family of proteins perform a critical role in the maintenance of membrane-associated complexes at points of intercellular contact in vertebrate cells. The protein encoded by this gene is predicted to resemble certain short C-terminal isoforms of dystrophin and dystrophin-related protein 1 (DRP1 or utrophin). DRP2 is expressed principally in the brain and spinal cord. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

DRP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30122715).

BS2

High Hemizygotes in GnomAdExome4 at 3 geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRP2	NM_001939.3 link	c.13G>A	p.Val5Ile	missense_variant	Exon 3 of 24	ENST00000395209.8	NP_001930.2	Q13474-1A0A024RCH3
DRP2	XM_047441894.1 link	c.13G>A	p.Val5Ile	missense_variant	Exon 2 of 23		XP_047297850.1
DRP2	XM_017029333.2 link	c.13G>A	p.Val5Ile	missense_variant	Exon 3 of 23		XP_016884822.1
DRP2	NM_001171184.2 link	c.-117-4200G>A		intron_variant	Intron 1 of 21		NP_001164655.1	Q13474-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRP2	ENST00000395209.8 link	c.13G>A	p.Val5Ile	missense_variant	Exon 3 of 24	1	NM_001939.3	ENSP00000378635.3		Q13474-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183296

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

67772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000365

AC:

AN:

1097074

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

362474

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Dec 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 5 of the DRP2 protein (p.Val5Ile). This variant is present in population databases (rs758131270, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with DRP2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

.;.;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.98

D;D;D

Vest4

0.43

MutPred

0.18

Loss of disorder (P = 0.1344);Loss of disorder (P = 0.1344);Loss of disorder (P = 0.1344);

MVP

0.32

MPC

1.0

ClinPred

0.54

GERP RS

5.8

Varity_R

0.23

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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