17-7313221-G-T

Variant names:

• chr17-7313221-G-T
• rs2270981
• NM_004489.5:c.795C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004489.5(GPS2):​c.795C>A​(p.Phe265Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GPS2 NM_004489.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3174237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPS2	NM_004489.5	c.795C>A	p.Phe265Leu	missense_variant	Exon 9 of 11	ENST00000380728.7	NP_004480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPS2	ENST00000380728.7	c.795C>A	p.Phe265Leu	missense_variant	Exon 9 of 11	1	NM_004489.5	ENSP00000370104.2
ENSG00000261915	ENST00000575474.1	n.*1070C>A		non_coding_transcript_exon_variant	Exon 17 of 19	5		ENSP00000468772.1
ENSG00000261915	ENST00000575474.1	n.*1070C>A		3_prime_UTR_variant	Exon 17 of 19	5		ENSP00000468772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;.;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.7	.;L;L
PhyloP100		2.4
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.70	.;N;N
REVEL	Benign	0.27
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0	D;T;T
Polyphen		0.010	.;B;B
Vest4		0.39
MutPred		0.19		.;Gain of phosphorylation at S266 (P = 0.1088);Gain of phosphorylation at S266 (P = 0.1088);
MVP		0.75
ClinPred		0.95	D
GERP RS		3.8
PromoterAI		-0.043	Neutral
Varity_R		0.52
gMVP		0.50

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: rs2270981; hg19: chr17-7216540;