X-102715734-A-G

Position:

chrX-102715734-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001004051.4(GPRASP2):c.865A>G(p.Ser289Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,210,368 control chromosomes in the GnomAD database, including 43 homozygotes. There are 649 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 23 hom., 316 hem., cov: 23)

Exomes 𝑓: 0.0012 ( 20 hom. 333 hem. )

Consequence

GPRASP2
NM_001004051.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0300

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018830895).

BP6

Variant X-102715734-A-G is Benign according to our data. Variant chrX-102715734-A-G is described in ClinVar as [Benign]. Clinvar id is 781553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1222/112109) while in subpopulation AFR AF= 0.0381 (1175/30843). AF 95% confidence interval is 0.0363. There are 23 homozygotes in gnomad4. There are 316 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRASP2	NM_001004051.4 linkuse as main transcript	c.865A>G	p.Ser289Gly	missense_variant	5/5	ENST00000483720.7
ARMCX5-GPRASP2	NR_146584.3 linkuse as main transcript	n.795+1468A>G		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.865A>G	p.Ser289Gly	missense_variant	5/5	2	NM_001004051.4	P1
ARMCX5-GPRASP2	ENST00000652409.1 linkuse as main transcript	c.-756+1468A>G		intron_variant				P1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1222

AN:

112057

Hom.:

Cov.:

AF XY:

0.00923

AC XY:

316

AN XY:

34229

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000372

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.00989

GnomAD3 exomes

AF:

0.00342

AC:

627

AN:

183500

Hom.:

AF XY:

0.00216

AC XY:

147

AN XY:

67932

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000721

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00154

GnomAD4 exome

AF:

0.00117

AC:

1288

AN:

1098259

Hom.:

Cov.:

AF XY:

0.000916

AC XY:

333

AN XY:

363613

show subpopulations

Gnomad4 AFR exome

AF:

0.0419

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.0109

AC:

1222

AN:

112109

Hom.:

Cov.:

AF XY:

0.00922

AC XY:

316

AN XY:

34291

show subpopulations

Gnomad4 AFR

AF:

0.0381

Gnomad4 AMR

AF:

0.00264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000373

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.00977

Alfa

AF:

0.000454

Hom.:

Bravo

AF:

0.0131

ESP6500AA

AF:

0.0386

AC:

148

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00390

AC:

473

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

GPRASP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 2019

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

0.043

BayesDel_addAF

Benign

-0.97

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.62

DANN

Benign

0.58

DEOGEN2

Benign

0.0019

T;T;T

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.12

.;T;.

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.6

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.48

N;N;N

REVEL

Benign

0.044

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.45

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.030

MVP

0.22

MPC

0.13

ClinPred

0.0036

GERP RS

1.3

Varity_R

0.036

gMVP

0.062

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