chrX-102714932-G-C

Position:

chrX-102714932-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004051.4(GPRASP2):c.63G>C(p.Glu21Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,211,335 control chromosomes in the GnomAD database, including 5 homozygotes. There are 889 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 45 hem., cov: 24)

Exomes 𝑓: 0.0025 ( 5 hom. 844 hem. )

Consequence

GPRASP2
NM_001004051.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.752

Variant links:

Genes affected

GPRASP2 (HGNC:25169): (G protein-coupled receptor associated sorting protein 2) The protein encoded by this gene is a member of a family that regulates the activity of G protein-coupled receptors (GPCRs). The encoded protein has been shown to be capable of interacting with several GPCRs, including the M1 muscarinic acetylcholine receptor and the calcitonin receptor. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

GPRASP2 links:

ARMCX5-GPRASP2 (HGNC:42000): (ARMCX5-GPRASP2 readthrough) This locus represents naturally occurring readthrough transcription among the adjacent armadillo repeat containing, X-linked 5 (ARMCX5), G protein-coupled receptor associated sorting proteins 1 and 2 (GPRASP1 and GPRASP2), basic helix-loop-helix family member b9 (BHLHB9), and long intergenic non-protein coding RNA 630 (LINC00630) genes on chromosome X. Transcripts may make use of multiple alternative promoters and polyadenylation signals in this region. Readthrough transcripts may produce proteins identical to the proteins encoded by GPRASP2 or BHLHB9. [provided by RefSeq, Apr 2017]

ARMCX5-GPRASP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074768364).

BS2

High Hemizygotes in GnomAd4 at 45 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRASP2	NM_001004051.4 linkuse as main transcript	c.63G>C	p.Glu21Asp	missense_variant	5/5	ENST00000483720.7
ARMCX5-GPRASP2	NR_146584.3 linkuse as main transcript	n.795+666G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRASP2	ENST00000483720.7 linkuse as main transcript	c.63G>C	p.Glu21Asp	missense_variant	5/5	2	NM_001004051.4	P1
ARMCX5-GPRASP2	ENST00000652409.1 linkuse as main transcript	c.-756+666G>C		intron_variant				P1

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

162

AN:

113100

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

35234

show subpopulations

Gnomad AFR

AF:

0.000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00102

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000635

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.00124

AC:

227

AN:

183363

Hom.:

AF XY:

0.00125

AC XY:

AN XY:

67813

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.000802

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000500

Gnomad NFE exome

AF:

0.00227

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.00246

AC:

2697

AN:

1098235

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

844

AN XY:

363589

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000739

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00305

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.00143

AC:

162

AN:

113100

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

35234

show subpopulations

Gnomad4 AFR

AF:

0.000321

Gnomad4 AMR

AF:

0.00102

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000635

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.00220

Hom.:

Bravo

AF:

0.00143

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00485

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00357

AC:

ExAC

AF:

0.00142

AC:

172

EpiCase

AF:

0.00245

EpiControl

AF:

0.00314

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.63G>C (p.E21D) alteration is located in exon 5 (coding exon 1) of the GPRASP2 gene. This alteration results from a G to C substitution at nucleotide position 63, causing the glutamic acid (E) at amino acid position 21 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

GPRASP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 16, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T;T

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.72

.;T;.

M_CAP

Benign

0.0057

MetaRNN

Benign

0.0075

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M;M

MutationTaster

Benign

0.95

N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.78

N;N;N

REVEL

Benign

0.027

Sift

Benign

0.071

T;T;T

Sift4G

Uncertain

0.025

D;D;D

Polyphen

0.82

P;P;P

Vest4

0.047

MutPred

0.12

Gain of ubiquitination at K16 (P = 0.1079);Gain of ubiquitination at K16 (P = 0.1079);Gain of ubiquitination at K16 (P = 0.1079);

MVP

0.30

MPC

0.35

ClinPred

0.013

GERP RS

2.6

Varity_R

0.12

gMVP

0.077

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

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