X-101231782-A-G

Variant names:

• chrX-101231782-A-G
• NM_001939.3:c.117+18A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001939.3(DRP2):​c.117+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000942 in 1,061,526 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: DRP2 NM_001939.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.03
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-101231782-A-G is Benign according to our data. Variant chrX-101231782-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1941750.Status of the report is criteria_provided_single_submitter, 1 stars.

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.117+18A>G		intron	N/A	NP_001930.2	Q13474-1
	DRP2	NM_001171184.2		c.-117-4078A>G		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.117+18A>G		intron	N/A	ENSP00000378635.3	Q13474-1
	DRP2	ENST00000402866.5	TSL:5	c.117+18A>G		intron	N/A	ENSP00000385038.1	Q13474-1
	DRP2	ENST00000538510.1	TSL:2	c.117+18A>G		intron	N/A	ENSP00000441051.1	Q13474-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.42e-7 AC: 1 AN: 1061526 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 330822

African (AFR) AF: 0.00 AC: 0 AN: 25662

American (AMR) AF: 0.00 AC: 0 AN: 34002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18530

East Asian (EAS) AF: 0.00 AC: 0 AN: 29967

South Asian (SAS) AF: 0.00 AC: 0 AN: 51411

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40263

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4012

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 812891

Other (OTH) AF: 0.00 AC: 0 AN: 44788

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.52
PhyloP100		1.0
PromoterAI		-0.0057	Neutral

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

hg19: chrX-100486771;