14-51950749-A-G

Variant names:

• chr14-51950749-A-G
• rs1188825967
• NM_053064.5:c.71A>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_053064.5(GNG2):​c.71A>G​(p.Asn24Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 1,455,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: GNG2 NM_053064.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.92

Genes affected

GNG2 (HGNC:4404): (G protein subunit gamma 2) This gene encodes one of the gamma subunits of a guanine nucleotide-binding protein. Such proteins are involved in signaling mechanisms across membranes. Various subunits forms heterodimers which then interact with the different signal molecules. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21489105).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNG2	NM_053064.5	c.71A>G	p.Asn24Ser	missense_variant	Exon 3 of 4	ENST00000556766.6	NP_444292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG2	ENST00000556766.6	c.71A>G	p.Asn24Ser	missense_variant	Exon 3 of 4	1	NM_053064.5	ENSP00000451231.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245620 Hom.: 0 AF XY: 0.00000752 AC XY: 1 AN XY: 133018

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1455520 Hom.: 0 Cov.: 29 AF XY: 0.00000967 AC XY: 7 AN XY: 724256

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000703

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.71A>G (p.N24S) alteration is located in exon 3 (coding exon 1) of the GNG2 gene. This alteration results from a A to G substitution at nucleotide position 71, causing the asparagine (N) at amino acid position 24 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Benign	0.88
DEOGEN2	Benign	0.0041	T;.;T;T;T;T;T;T;T;.
Eigen	Benign	-0.080
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T;T;D;T;.;.;.;.;.;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.75	N;N;D;.;N;N;N;N;N;D
REVEL	Benign	0.070
Sift	Benign	0.64	T;T;.;.;T;T;T;T;T;T
Sift4G	Benign	0.65	T;T;D;T;T;T;T;T;T;D
Polyphen		0.0030	.;.;.;B;B;B;B;B;B;.
Vest4		0.56
MutPred		0.35		.;.;Gain of phosphorylation at N24 (P = 0.0222);Gain of phosphorylation at N24 (P = 0.0222);Gain of phosphorylation at N24 (P = 0.0222);Gain of phosphorylation at N24 (P = 0.0222);Gain of phosphorylation at N24 (P = 0.0222);Gain of phosphorylation at N24 (P = 0.0222);Gain of phosphorylation at N24 (P = 0.0222);.;
MVP		0.35
MPC		0.85
ClinPred		0.72	D
GERP RS		5.0
Varity_R		0.29
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs1188825967; hg19: chr14-52417467;