rs8015138

Positions:

• chr14-51843386-A-C
• chr14-51843386-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001389707.1(GNG2):​c.-71+15579A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,784 control chromosomes in the GnomAD database, including 12,698 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 0.38 (12698 hom., cov: 30)
• Consequence: GNG2 NM_001389707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG2	NM_001389707.1	c.-71+15579A>C		intron_variant			NP_001376636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNG2	ENST00000553432.5	c.64+15579A>C		intron_variant		4		ENSP00000451279
GNG2	ENST00000557376.5	c.88+1814A>C		intron_variant		4		ENSP00000450758
GNG2	ENST00000556522.5	c.64+15579A>C		intron_variant, NMD_transcript_variant		4		ENSP00000450904

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58211 AN: 151666 Hom.: 12697 Cov.: 30

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.384 AC: 58218 AN: 151784 Hom.: 12698 Cov.: 30 AF XY: 0.378 AC XY: 28041 AN XY: 74178

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.408

Alfa AF: 0.417 Hom.: 1802

Bravo AF: 0.371

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	7.6
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8015138; hg19: chr14-52310104;