X-101231732-AG-A

Position:

• chrX-101231732-AG-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_Strong BS2_Supporting

The NM_001939.3(DRP2):​c.86del​(p.Ser29ThrfsTer31) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,097,863 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000036 (0 hom. 2 hem.)
• Consequence: DRP2 NM_001939.3 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:2
• Conservation: PhyloP100: 2.32

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 3 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.97 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• BS2: High Hemizygotes in GnomAdExome4 at 2 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/exons	MANE	Protein	UniProt
DRP2	NM_001939.3	c.86del	p.Ser29ThrfsTer31	frameshift_variant	3/24	ENST00000395209.8	NP_001930.2
DRP2	XM_047441894.1	c.86del	p.Ser29ThrfsTer31	frameshift_variant	2/23		XP_047297850.1
DRP2	XM_017029333.2	c.86del	p.Ser29ThrfsTer31	frameshift_variant	3/23		XP_016884822.1
DRP2	NM_001171184.2	c.-117-4127del		intron_variant			NP_001164655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRP2	ENST00000395209.8	c.86del	p.Ser29ThrfsTer31	frameshift_variant	3/24	1	NM_001939.3	ENSP00000378635	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1097863 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 2 AN XY: 363235

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000475

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:2

Uncertain significance, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100486721;