Variant chr22-31400695-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_004147.4(DRG1):c.118C>T(p.Arg40*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)

Consequence

DRG1
NM_004147.4 stop_gained

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

DRG1 (HGNC:3029): (developmentally regulated GTP binding protein 1) Enables several functions, including GTPase activity; identical protein binding activity; and potassium ion binding activity. Involved in positive regulation of microtubule polymerization and regulation of mitotic spindle assembly. Located in cytosol and nuclear body. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

DRG1 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-31400695-C-T is Pathogenic according to our data. Variant chr22-31400695-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 816815.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRG1	NM_004147.4 link	c.118C>T	p.Arg40*	stop_gained	2/9	ENST00000331457.9	NP_004138.1	Q9Y295

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DRG1	ENST00000331457.9 link	c.118C>T	p.Arg40*	stop_gained	2/9	1	NM_004147.4	ENSP00000329715.4	Q9Y295
DRG1	ENST00000416465.5 link	n.118C>T		non_coding_transcript_exon_variant	2/6	5		ENSP00000408091.1	F8WEE0
DRG1	ENST00000433341.5 link	n.185C>T		non_coding_transcript_exon_variant	2/7	3
DRG1	ENST00000486584.1 link	n.93+970C>T		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251186

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Flexion contracture

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.49

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.63

Vest4

0.86

GERP RS

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over