rs5921756

chrX-101237784-G-AchrX-101237784-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001939.3(DRP2):c.438+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 1,121,122 control chromosomes in the GnomAD database, including 3,521 homozygotes. There are 31,929 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (449 hom., 3089 hem., cov: 22)
  • Exomes 𝑓: 0.091 (3072 hom. 28840 hem.)
• Consequence: DRP2 NM_001939.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.580

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant X-101237784-G-A is Benign according to our data. Variant chrX-101237784-G-A is described in ClinVar as [Benign]. Clinvar id is 1273592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-101237784-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRP2	NM_001939.3	c.438+9G>A		intron_variant		ENST00000395209.8
DRP2	NM_001171184.2	c.204+9G>A		intron_variant
DRP2	XM_017029333.2	c.438+9G>A		intron_variant
DRP2	XM_047441894.1	c.438+9G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRP2	ENST00000395209.8	c.438+9G>A		intron_variant		1	NM_001939.3	P1

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 11119 AN: 111277 Hom.: 447 Cov.: 22 AF XY: 0.0919 AC XY: 3078 AN XY: 33495

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.00225

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.0501

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.0810 AC: 11859 AN: 146494 Hom.: 458 AF XY: 0.0859 AC XY: 3499 AN XY: 40726

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.0330

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.000522

Gnomad SAS exome AF: 0.0870

Gnomad FIN exome AF: 0.0602

Gnomad NFE exome AF: 0.0989

Gnomad OTH exome AF: 0.0871

GnomAD4 exome AF: 0.0914 AC: 92300 AN: 1009789 Hom.: 3072 Cov.: 30 AF XY: 0.0933 AC XY: 28840 AN XY: 309097

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.0946

Gnomad4 EAS exome AF: 0.000388

Gnomad4 SAS exome AF: 0.0972

Gnomad4 FIN exome AF: 0.0606

Gnomad4 NFE exome AF: 0.0959

Gnomad4 OTH exome AF: 0.0916

GnomAD4 genome AF: 0.100 AC: 11134 AN: 111333 Hom.: 449 Cov.: 22 AF XY: 0.0920 AC XY: 3089 AN XY: 33561

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0567

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.00226

Gnomad4 SAS AF: 0.0876

Gnomad4 FIN AF: 0.0501

Gnomad4 NFE AF: 0.0991

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0899 Hom.: 1830

Bravo AF: 0.104

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	11
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs5921756; hg19: chrX-100492773;