chr14-51904294-G-C

Position:

• chr14-51904294-G-C

Variant summary

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

The NM_053064.5(GNG2):​c.-30+26637G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,108 control chromosomes in the GnomAD database, including 2,900 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 0.14 (2900 hom., cov: 32)
• Consequence: GNG2 NM_053064.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG2	NM_053064.5	c.-30+26637G>C		intron_variant		ENST00000556766.6	NP_444292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNG2	ENST00000556766.6	c.-30+26637G>C		intron_variant		1	NM_053064.5	ENSP00000451231	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21024 AN: 151990 Hom.: 2882 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0340

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0528

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.139 AC: 21090 AN: 152108 Hom.: 2900 Cov.: 32 AF XY: 0.135 AC XY: 10058 AN XY: 74378

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.0339

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.0571

Gnomad4 NFE AF: 0.0528

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0321 Hom.: 19

Bravo AF: 0.148

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.83

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: rs11851703; hg19: chr14-52371012;