X-101235872-G-T

Variant names:

• chrX-101235872-G-T
• NM_001939.3:c.130G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001939.3(DRP2):​c.130G>T​(p.Val44Phe) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: DRP2 NM_001939.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0580

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043258727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRP2	NM_001939.3	c.130G>T	p.Val44Phe	missense_variant	Exon 4 of 24	ENST00000395209.8	NP_001930.2
DRP2	XM_047441894.1	c.130G>T	p.Val44Phe	missense_variant	Exon 3 of 23		XP_047297850.1
DRP2	XM_017029333.2	c.130G>T	p.Val44Phe	missense_variant	Exon 4 of 23		XP_016884822.1
DRP2	NM_001171184.2	c.-105G>T		5_prime_UTR_variant	Exon 2 of 22		NP_001164655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRP2	ENST00000395209.8	c.130G>T	p.Val44Phe	missense_variant	Exon 4 of 24	1	NM_001939.3	ENSP00000378635.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.130G>T (p.V44F) alteration is located in exon 4 (coding exon 2) of the DRP2 gene. This alteration results from a G to T substitution at nucleotide position 130, causing the valine (V) at amino acid position 44 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.3
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T;T;T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.74	.;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;L;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.59	N;N;N
REVEL	Benign	0.075
Sift	Uncertain	0.017	D;D;D
Sift4G	Uncertain	0.023	D;D;D
Polyphen		0.037	B;B;B
Vest4		0.23
MutPred		0.085		Loss of glycosylation at T45 (P = 0.1134);Loss of glycosylation at T45 (P = 0.1134);Loss of glycosylation at T45 (P = 0.1134);
MVP		0.24
MPC		0.54
ClinPred		0.084	T
GERP RS		0.19
Varity_R		0.12
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100490861;