dbSNP rs61097741: GPRASP2:p.Ala128_Gln131del (chrX-102715243-AGGCCCAGGCATG-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_001004051.4(GPRASP2):c.382_393delGCATGGGCCCAG(p.Ala128_Gln131del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,211,879 control chromosomes in the GnomAD database, including 18 homozygotes. There are 451 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 10 hom., 226 hem., cov: 24)

Exomes 𝑓: 0.00075 ( 8 hom. 225 hem. )

Consequence

GPRASP2
NM_001004051.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.407

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001004051.4.

BP6

Variant X-102715243-AGGCCCAGGCATG-A is Benign according to our data. Variant chrX-102715243-AGGCCCAGGCATG-A is described in ClinVar as Benign. ClinVar VariationId is 787162.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00743 (844/113645) while in subpopulation AFR AF = 0.0259 (813/31382). AF 95% confidence interval is 0.0244. There are 10 homozygotes in GnomAd4. There are 226 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPRASP2	NM_001004051.4	MANE Select	c.382_393delGCATGGGCCCAG	p.Ala128_Gln131del	conservative_inframe_deletion	Exon 5 of 5	NP_001004051.1	Q96D09
GPRASP2	NM_001184874.3		c.382_393delGCATGGGCCCAG	p.Ala128_Gln131del	conservative_inframe_deletion	Exon 5 of 5	NP_001171803.1	Q96D09
GPRASP2	NM_001184875.3		c.382_393delGCATGGGCCCAG	p.Ala128_Gln131del	conservative_inframe_deletion	Exon 4 of 4	NP_001171804.1	Q96D09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPRASP2	ENST00000483720.7	TSL:2 MANE Select	c.382_393delGCATGGGCCCAG	p.Ala128_Gln131del	conservative_inframe_deletion	Exon 5 of 5	ENSP00000507692.1	Q96D09
GPRASP2	ENST00000332262.10	TSL:1	c.382_393delGCATGGGCCCAG	p.Ala128_Gln131del	conservative_inframe_deletion	Exon 4 of 4	ENSP00000339057.3	Q96D09
ARMCX5-GPRASP2	ENST00000652409.1		c.-756+985_-756+996delGCATGGGCCCAG		intron	N/A	ENSP00000498643.1

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

846

AN:

113593

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00193

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000935

Gnomad OTH

AF:

0.00325

GnomAD2 exomes

AF:

0.00201

AC:

367

AN:

183022

AF XY:

0.00124

show subpopulations

Gnomad AFR exome

AF:

0.0256

Gnomad AMR exome

AF:

0.000766

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000490

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000755

AC:

829

AN:

1098234

Hom.:

AF XY:

0.000619

AC XY:

225

AN XY:

363592

show subpopulations

African (AFR)

AF:

0.0264

AC:

696

AN:

26402

American (AMR)

AF:

0.000937

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.000111

AC:

AN:

54149

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40510

Middle Eastern (MID)

AF:

0.00145

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000950

AC:

AN:

842142

Other (OTH)

AF:

0.00174

AC:

AN:

46097

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00743

AC:

844

AN:

113645

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

226

AN XY:

35781

show subpopulations

African (AFR)

AF:

0.0259

AC:

813

AN:

31382

American (AMR)

AF:

0.00193

AC:

AN:

10884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2663

East Asian (EAS)

AF:

0.00

AC:

AN:

3588

South Asian (SAS)

AF:

0.00

AC:

AN:

2814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6381

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000935

AC:

AN:

53468

Other (OTH)

AF:

0.00321

AC:

AN:

1557

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00381

Hom.:

Bravo

AF:

0.00866

Asia WGS

AF:

0.000796

AC:

AN:

2522

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.41

Mutation Taster

=198/2

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over