X-102714835-G-A

Position:

• chrX-102714835-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001004051.4(GPRASP2):​c.-35G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,180,372 control chromosomes in the GnomAD database, including 41 homozygotes. There are 870 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (4 hom., 91 hem., cov: 24)
  • Exomes 𝑓: 0.0022 (37 hom. 779 hem.)
• Consequence: GPRASP2 NM_001004051.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.66

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-102714835-G-A is Benign according to our data. Variant chrX-102714835-G-A is described in ClinVar as [Benign]. Clinvar id is 1280293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00283 (320/113058) while in subpopulation EAS AF= 0.0487 (174/3574). AF 95% confidence interval is 0.0428. There are 4 homozygotes in gnomad4. There are 91 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPRASP2	NM_001004051.4	c.-35G>A		5_prime_UTR_variant	5/5	ENST00000483720.7
ARMCX5-GPRASP2	NR_146584.3	n.795+569G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPRASP2	ENST00000483720.7	c.-35G>A		5_prime_UTR_variant	5/5	2	NM_001004051.4	P1
ARMCX5-GPRASP2	ENST00000652409.1	c.-756+569G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.00284 AC: 321 AN: 113004 Hom.: 4 Cov.: 24 AF XY: 0.00262 AC XY: 92 AN XY: 35128

Gnomad AFR AF: 0.000867

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00652

Gnomad ASJ AF: 0.00754

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.00180

Gnomad FIN AF: 0.000160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000299

Gnomad OTH AF: 0.00461

GnomAD3 exomes AF: 0.00671 AC: 1023 AN: 152549 Hom.: 11 AF XY: 0.00611 AC XY: 298 AN XY: 48743

Gnomad AFR exome AF: 0.000564

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00704

Gnomad EAS exome AF: 0.0545

Gnomad SAS exome AF: 0.000667

Gnomad FIN exome AF: 0.0000713

Gnomad NFE exome AF: 0.000170

Gnomad OTH exome AF: 0.00388

GnomAD4 exome AF: 0.00218 AC: 2329 AN: 1067314 Hom.: 37 Cov.: 31 AF XY: 0.00225 AC XY: 779 AN XY: 345802

Gnomad4 AFR exome AF: 0.000356

Gnomad4 AMR exome AF: 0.0118

Gnomad4 ASJ exome AF: 0.00783

Gnomad4 EAS exome AF: 0.0507

Gnomad4 SAS exome AF: 0.00115

Gnomad4 FIN exome AF: 0.0000510

Gnomad4 NFE exome AF: 0.0000700

Gnomad4 OTH exome AF: 0.00434

GnomAD4 genome AF: 0.00283 AC: 320 AN: 113058 Hom.: 4 Cov.: 24 AF XY: 0.00259 AC XY: 91 AN XY: 35192

Gnomad4 AFR AF: 0.000865

Gnomad4 AMR AF: 0.00651

Gnomad4 ASJ AF: 0.00754

Gnomad4 EAS AF: 0.0487

Gnomad4 SAS AF: 0.00181

Gnomad4 FIN AF: 0.000160

Gnomad4 NFE AF: 0.000300

Gnomad4 OTH AF: 0.00455

Alfa AF: 0.00257 Hom.: 33

Bravo AF: 0.00404

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	May 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.087
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs2235805; hg19: chrX-101969763; COSMIC: COSV59992609; COSMIC: COSV59992609;