chrX-101231709-C-A

Variant names:

• chrX-101231709-C-A
• NM_001939.3:c.62C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001939.3(DRP2):​c.62C>A​(p.Ala21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: DRP2 NM_001939.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.118
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09596178).

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.62C>A	p.Ala21Glu	missense	Exon 3 of 24	NP_001930.2	Q13474-1
	DRP2	NM_001171184.2		c.-117-4151C>A		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.62C>A	p.Ala21Glu	missense	Exon 3 of 24	ENSP00000378635.3	Q13474-1
	DRP2	ENST00000402866.5	TSL:5	c.62C>A	p.Ala21Glu	missense	Exon 3 of 24	ENSP00000385038.1	Q13474-1
	DRP2	ENST00000538510.1	TSL:2	c.62C>A	p.Ala21Glu	missense	Exon 1 of 22	ENSP00000441051.1	Q13474-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

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	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0089	T
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.12
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.067
Sift	Benign	0.073	T
Sift4G	Benign	0.061	T
Polyphen		0.28	B
Vest4		0.25
MutPred		0.19		Gain of solvent accessibility (P = 0.1319)
MVP		0.50
MPC		0.47
ClinPred		0.37	T
GERP RS		5.0
PromoterAI		0.046	Neutral
Varity_R		0.23
gMVP		0.43
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chrX-100486698;