17-7314144-T-C

Variant names:

• chr17-7314144-T-C
• rs2292064
• NM_004489.5:c.333A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004489.5(GPS2):​c.333A>G​(p.Leu111Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,612,252 control chromosomes in the GnomAD database, including 238,538 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (21240 hom., cov: 31)
  • Exomes 𝑓: 0.54 (217298 hom.)
• Consequence: GPS2 NM_004489.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 32 publications found

Genes affected

GPS2 (HGNC:4550): (G protein pathway suppressor 2) This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function. [provided by RefSeq, Jul 2008]

ENSG00000261915 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=1.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004489.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPS2	NM_004489.5	MANE Select	c.333A>G	p.Leu111Leu	synonymous	Exon 5 of 11	NP_004480.1	Q13227-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPS2	ENST00000380728.7	TSL:1 MANE Select	c.333A>G	p.Leu111Leu	synonymous	Exon 5 of 11	ENSP00000370104.2	Q13227-1
	GPS2	ENST00000389167.9	TSL:1	c.333A>G	p.Leu111Leu	synonymous	Exon 4 of 10	ENSP00000379841.4	Q13227-1
	GPS2	ENST00000571569.5	TSL:1	n.838A>G		non_coding_transcript_exon	Exon 4 of 10

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79635 AN: 151784 Hom.: 21200 Cov.: 31

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.513

GnomAD2 exomes AF: 0.563 AC: 141453 AN: 251466 AF XY: 0.558

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.693

Gnomad ASJ exome AF: 0.442

Gnomad EAS exome AF: 0.658

Gnomad FIN exome AF: 0.604

Gnomad NFE exome AF: 0.517

Gnomad OTH exome AF: 0.533

GnomAD4 exome AF: 0.542 AC: 791883 AN: 1460350 Hom.: 217298 Cov.: 38 AF XY: 0.542 AC XY: 393877 AN XY: 726572

African (AFR) AF: 0.473 AC: 15806 AN: 33444

American (AMR) AF: 0.681 AC: 30444 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 11527 AN: 26126

East Asian (EAS) AF: 0.679 AC: 26936 AN: 39690

South Asian (SAS) AF: 0.593 AC: 51120 AN: 86216

European-Finnish (FIN) AF: 0.602 AC: 32171 AN: 53420

Middle Eastern (MID) AF: 0.414 AC: 2390 AN: 5768

European-Non Finnish (NFE) AF: 0.530 AC: 589124 AN: 1110636

Other (OTH) AF: 0.536 AC: 32365 AN: 60328

GnomAD4 genome AF: 0.525 AC: 79730 AN: 151902 Hom.: 21240 Cov.: 31 AF XY: 0.530 AC XY: 39324 AN XY: 74230

African (AFR) AF: 0.468 AC: 19367 AN: 41394

American (AMR) AF: 0.589 AC: 8986 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3470

East Asian (EAS) AF: 0.671 AC: 3470 AN: 5168

South Asian (SAS) AF: 0.607 AC: 2918 AN: 4808

European-Finnish (FIN) AF: 0.599 AC: 6328 AN: 10560

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35476 AN: 67928

Other (OTH) AF: 0.514 AC: 1086 AN: 2112

Alfa AF: 0.512 Hom.: 32227

Bravo AF: 0.522

Asia WGS AF: 0.618 AC: 2147 AN: 3478

EpiCase AF: 0.498

EpiControl AF: 0.488

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		1.4
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2292064; hg19: chr17-7217463; COSMIC: COSV59747661; COSMIC: COSV59747661;