X-101231523-G-A

Position:

• chrX-101231523-G-A

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.-63-62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00809 in 633,725 control chromosomes in the GnomAD database, including 183 homozygotes. There are 1,316 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (110 hom., 804 hem., cov: 22)
  • Exomes 𝑓: 0.0040 (73 hom. 512 hem.)
• Consequence: DRP2 NM_001939.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.707

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=-0.66).
• BP6: Variant X-101231523-G-A is Benign according to our data. Variant chrX-101231523-G-A is described in ClinVar as [Benign]. Clinvar id is 1229685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRP2	NM_001939.3	c.-63-62G>A		intron_variant		ENST00000395209.8	NP_001930.2
DRP2	NM_001171184.2	c.-117-4337G>A		intron_variant			NP_001164655.1
DRP2	XM_017029333.2	c.-63-62G>A		intron_variant			XP_016884822.1
DRP2	XM_047441894.1	c.-63-62G>A		intron_variant			XP_047297850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRP2	ENST00000395209.8	c.-63-62G>A		intron_variant		1	NM_001939.3	ENSP00000378635	P1

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 3037 AN: 111876 Hom.: 111 Cov.: 22 AF XY: 0.0236 AC XY: 802 AN XY: 34038

Gnomad AFR AF: 0.0933

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000374

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.000376

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.00400 AC: 2089 AN: 521795 Hom.: 73 Cov.: 8 AF XY: 0.00294 AC XY: 512 AN XY: 174257

Gnomad4 AFR exome AF: 0.0984

Gnomad4 AMR exome AF: 0.00611

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000529

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000317

Gnomad4 OTH exome AF: 0.00914

GnomAD4 genome AF: 0.0272 AC: 3039 AN: 111930 Hom.: 110 Cov.: 22 AF XY: 0.0236 AC XY: 804 AN XY: 34102

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000357

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0185 Hom.: 56

Bravo AF: 0.0321

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.78

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: rs143057116; hg19: chrX-100486512;