X-101231742-G-T

Variant names:

• chrX-101231742-G-T
• rs201882686
• NM_001939.3:c.95G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001939.3(DRP2):​c.95G>T​(p.Arg32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: DRP2 NM_001939.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRP2	NM_001939.3	c.95G>T	p.Arg32Leu	missense_variant	Exon 3 of 24	ENST00000395209.8	NP_001930.2
DRP2	XM_047441894.1	c.95G>T	p.Arg32Leu	missense_variant	Exon 2 of 23		XP_047297850.1
DRP2	XM_017029333.2	c.95G>T	p.Arg32Leu	missense_variant	Exon 3 of 23		XP_016884822.1
DRP2	NM_001171184.2	c.-117-4118G>T		intron_variant	Intron 1 of 21		NP_001164655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRP2	ENST00000395209.8	c.95G>T	p.Arg32Leu	missense_variant	Exon 3 of 24	1	NM_001939.3	ENSP00000378635.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;T;T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	.;.;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.078
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.020	D;D;D
Polyphen		0.039	B;B;B
Vest4		0.41
MutPred		0.27		Loss of methylation at R32 (P = 0.0761);Loss of methylation at R32 (P = 0.0761);Loss of methylation at R32 (P = 0.0761);
MVP		0.44
MPC		0.50
ClinPred		0.64	D
GERP RS		4.8
Varity_R		0.24
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.45		Position offset: 22

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201882686; hg19: chrX-100486731;