rs1922312726

Variant names:

• chrX-101231659-G-T
• rs1922312726
• NM_001939.3:c.12G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001939.3(DRP2):​c.12G>T​(p.Met4Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 111,042 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M4V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
• Consequence: DRP2 NM_001939.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001939.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRP2	NM_001939.3	MANE Select	c.12G>T	p.Met4Ile	missense	Exon 3 of 24	NP_001930.2	Q13474-1
	DRP2	NM_001171184.2		c.-117-4201G>T		intron	N/A	NP_001164655.1	Q13474-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRP2	ENST00000395209.8	TSL:1 MANE Select	c.12G>T	p.Met4Ile	missense	Exon 3 of 24	ENSP00000378635.3	Q13474-1
	DRP2	ENST00000402866.5	TSL:5	c.12G>T	p.Met4Ile	missense	Exon 3 of 24	ENSP00000385038.1	Q13474-1
	DRP2	ENST00000538510.1	TSL:2	c.12G>T	p.Met4Ile	missense	Exon 1 of 22	ENSP00000441051.1	Q13474-1

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111042 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000328

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000388

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111042 Hom.: 0 Cov.: 22 AF XY: 0.0000301 AC XY: 1 AN XY: 33250

African (AFR) AF: 0.0000328 AC: 1 AN: 30489

American (AMR) AF: 0.00 AC: 0 AN: 10431

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3526

South Asian (SAS) AF: 0.000388 AC: 1 AN: 2579

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52944

Other (OTH) AF: 0.00 AC: 0 AN: 1480

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0096	T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.18
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.050	T
Polyphen		0.015	B
Vest4		0.28
MutPred		0.34		Loss of disorder (P = 0.0036)
MVP		0.24
MPC		0.45
ClinPred		0.78	D
GERP RS		5.8
PromoterAI		0.013	Neutral
Varity_R		0.52
gMVP		0.55
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: 10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1922312726; hg19: chrX-100486648;