rs12028832

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013296.5(GPSM2):c.557+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,611,010 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 80 hom., cov: 32)

Exomes 𝑓: 0.014 ( 323 hom. )

Consequence

GPSM2
NM_013296.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.460

Publications

2 publications found

Variant links:

Genes affected

GPSM2 (HGNC:29501): (G protein signaling modulator 2) The protein encoded by this gene belongs to a family of proteins that modulate activation of G proteins, which transduce extracellular signals received by cell surface receptors into integrated cellular responses. The N-terminal half of this protein contains 10 copies of leu-gly-asn (LGN) repeat, and the C-terminal half contains 4 GoLoco motifs, which are involved in guanine nucleotide exchange. This protein may play a role in neuroblast division and in the development of normal hearing. Mutations in this gene are associated with autosomal recessive nonsyndromic deafness (DFNB82). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

GPSM2 links:

CLCC1 (HGNC:29675): (chloride channel CLIC like 1) Predicted to enable chloride channel activity. Predicted to be involved in chloride transport. Located in endoplasmic reticulum and mitochondria-associated endoplasmic reticulum membrane. Implicated in retinitis pigmentosa 32. [provided by Alliance of Genome Resources, Apr 2022]

CLCC1 links:

AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

AKNAD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-108898118-A-G is Benign according to our data. Variant chr1-108898118-A-G is described in ClinVar as [Benign]. Clinvar id is 260281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM2	NM_013296.5 link	c.557+17A>G		intron_variant	Intron 5 of 14	ENST00000264126.9	NP_037428.3	P81274A0A024R0F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPSM2	ENST00000264126.9 link	c.557+17A>G		intron_variant	Intron 5 of 14	1	NM_013296.5	ENSP00000264126.3		P81274

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3750

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0551

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.0586

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00998

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.0188

AC:

4718

AN:

251082

AF XY:

0.0199

show subpopulations

Gnomad AFR exome

AF:

0.0554

Gnomad AMR exome

AF:

0.00980

Gnomad ASJ exome

AF:

0.0276

Gnomad EAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0135

AC:

19695

AN:

1458706

Hom.:

323

Cov.:

AF XY:

0.0147

AC XY:

10654

AN XY:

725948

show subpopulations

African (AFR)

AF:

0.0571

AC:

1906

AN:

33398

American (AMR)

AF:

0.0109

AC:

489

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0273

AC:

713

AN:

26106

East Asian (EAS)

AF:

0.0155

AC:

614

AN:

39676

South Asian (SAS)

AF:

0.0518

AC:

4462

AN:

86168

European-Finnish (FIN)

AF:

0.00197

AC:

105

AN:

53412

Middle Eastern (MID)

AF:

0.0350

AC:

201

AN:

5750

European-Non Finnish (NFE)

AF:

0.00910

AC:

10096

AN:

1109222

Other (OTH)

AF:

0.0184

AC:

1109

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

942

1885

2827

3770

4712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0248

AC:

3776

AN:

152304

Hom.:

Cov.:

AF XY:

0.0254

AC XY:

1892

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0556

AC:

2310

AN:

41550

American (AMR)

AF:

0.0167

AC:

255

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3468

East Asian (EAS)

AF:

0.0133

AC:

AN:

5190

South Asian (SAS)

AF:

0.0582

AC:

281

AN:

4828

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0100

AC:

680

AN:

68026

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

186

372

559

745

931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0163

Hom.:

Bravo

AF:

0.0262

Asia WGS

AF:

0.0420

AC:

145

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 14, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.9

(source)

DANN

Benign

0.56

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs12028832

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over