14-51889945-A-G

Position:

• chr14-51889945-A-G

Variant summary

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

The ENST00000556766.6(GNG2):​c.-30+12288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,164 control chromosomes in the GnomAD database, including 4,039 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 0.18 (4039 hom., cov: 32)
• Consequence: GNG2 ENST00000556766.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG2	NM_053064.5	c.-30+12288A>G		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+12288A>G		intron_variant		1	NM_053064.5	ENSP00000451231	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26696 AN: 152046 Hom.: 4026 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0711

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.176 AC: 26745 AN: 152164 Hom.: 4039 Cov.: 32 AF XY: 0.178 AC XY: 13241 AN XY: 74400

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.0711

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.0851

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0570

Gnomad4 OTH AF: 0.153

Alfa AF: 0.111 Hom.: 442

Bravo AF: 0.187

Asia WGS AF: 0.147 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.9
DANN	Benign	0.80

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: rs7154422; hg19: chr14-52356663;