14-51889945-A-G

Variant names:

• chr14-51889945-A-G
• rs7154422
• NM_053064.5:c.-30+12288A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053064.5(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 NM_053064.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GNG2	NM_053064.5	c.-30+12288A>G		intron_variant	Intron 2 of 3	ENST00000556766.6	NP_444292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG2	ENST00000556766.6	c.-30+12288A>G		intron_variant	Intron 2 of 3	1	NM_053064.5	ENSP00000451231.1

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

African (AFR) AF: 0.409 AC: 16942 AN: 41472

American (AMR) AF: 0.164 AC: 2505 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0711 AC: 247 AN: 3472

East Asian (EAS) AF: 0.196 AC: 1016 AN: 5186

South Asian (SAS) AF: 0.0851 AC: 411 AN: 4832

European-Finnish (FIN) AF: 0.130 AC: 1375 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0570 AC: 3874 AN: 68006

Other (OTH) AF: 0.153 AC: 324 AN: 2112

Alfa AF: 0.108 Hom.: 702

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7154422; hg19: chr14-52356663;