NM_001939.3:c.438+9G>A

Variant names:

• chrX-101237784-G-A
• rs5921756
• NM_001939.3:c.438+9G>A

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -0.580
• Publications: 5 publications found

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]

DRP2 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: XL Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1273592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRP2	NM_001939.3	c.438+9G>A		intron_variant	Intron 5 of 23	ENST00000395209.8	NP_001930.2
DRP2	NM_001171184.2	c.204+9G>A		intron_variant	Intron 3 of 21		NP_001164655.1
DRP2	XM_047441894.1	c.438+9G>A		intron_variant	Intron 4 of 22		XP_047297850.1
DRP2	XM_017029333.2	c.438+9G>A		intron_variant	Intron 5 of 22		XP_016884822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DRP2	ENST00000395209.8	c.438+9G>A		intron_variant	Intron 5 of 23	1	NM_001939.3	ENSP00000378635.3

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 11119 AN: 111277 Hom.: 447 Cov.: 22

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

GnomAD2 exomes AF: 0.0810 AC: 11859 AN: 146494 AF XY: 0.0859

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 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

African (AFR) AF: 0.147 AC: 3635 AN: 24656

American (AMR) AF: 0.0396 AC: 1158 AN: 29274

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 1590 AN: 16809

East Asian (EAS) AF: 0.000388 AC: 11 AN: 28350

South Asian (SAS) AF: 0.0972 AC: 3582 AN: 36850

European-Finnish (FIN) AF: 0.0606 AC: 2305 AN: 38031

Middle Eastern (MID) AF: 0.119 AC: 371 AN: 3106

European-Non Finnish (NFE) AF: 0.0959 AC: 75816 AN: 790860

Other (OTH) AF: 0.0916 AC: 3832 AN: 41853

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

African (AFR) AF: 0.135 AC: 4130 AN: 30551

American (AMR) AF: 0.0567 AC: 597 AN: 10531

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 253 AN: 2644

East Asian (EAS) AF: 0.00226 AC: 8 AN: 3545

South Asian (SAS) AF: 0.0876 AC: 230 AN: 2626

European-Finnish (FIN) AF: 0.0501 AC: 303 AN: 6048

Middle Eastern (MID) AF: 0.117 AC: 25 AN: 214

European-Non Finnish (NFE) AF: 0.0991 AC: 5252 AN: 52982

Other (OTH) AF: 0.101 AC: 154 AN: 1523

Alfa AF: 0.0935 Hom.: 2776

Bravo AF: 0.104

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5921756; hg19: chrX-100492773;