chr11-64934789-C-A

Variant names:

• chr11-64934789-C-A
• rs573463788
• NM_130769.4:c.374G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_130769.4(GPHA2):​c.374G>T​(p.Arg125Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R125P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GPHA2 NM_130769.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90
• Publications: 2 publications found

Genes affected

GPHA2 (HGNC:18054): (glycoprotein hormone subunit alpha 2) GPHA2 is a cystine knot-forming polypeptide and a subunit of the dimeric glycoprotein hormone family (Hsu et al., 2002 [PubMed 12089349]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130769.4. 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
	GPHA2	NM_130769.4	MANE Select	c.374G>T	p.Arg125Leu	missense	Exon 4 of 4	NP_570125.1	Q96T91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPHA2	ENST00000279168.7	TSL:1 MANE Select	c.374G>T	p.Arg125Leu	missense	Exon 4 of 4	ENSP00000279168.2	Q96T91
	GPHA2	ENST00000533257.1	TSL:2	c.374G>T	p.Arg125Leu	missense	Exon 3 of 3	ENSP00000432918.1	Q96T91
	GPHA2	ENST00000532246.1	TSL:3	c.*133G>T		downstream_gene	N/A	ENSP00000431352.1	E9PLQ0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.21
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.45		Loss of MoRF binding (P = 0.0031)
MVP		0.37
MPC		1.0
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.48
gMVP		0.70
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs573463788; hg19: chr11-64702261;