rs4468527

Positions:

• chr14-51858413-A-G
• chr14-51858413-A-T

Variant summary

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

The ENST00000553299.5(GNG2):​n.145+11035A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,252 control chromosomes in the GnomAD database, including 62,011 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 0.90 (62011 hom., cov: 32)
• Consequence: GNG2 ENST00000553299.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG2	NM_001389707.1	c.-70-19204A>G		intron_variant			NP_001376636.1
GNG2	NM_001389708.1	c.-71+11035A>G		intron_variant			NP_001376637.1
GNG2	NM_001389709.1	c.-71+826A>G		intron_variant			NP_001376638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNG2	ENST00000553299.5	n.145+11035A>G		intron_variant, non_coding_transcript_variant		1
GNG2	ENST00000553432.5	c.64+30606A>G		intron_variant		4		ENSP00000451279
GNG2	ENST00000553560.5	c.-71+11035A>G		intron_variant		3		ENSP00000450586

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137257 AN: 152134 Hom.: 61965 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.896

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

GnomAD4 genome AF: 0.902 AC: 137360 AN: 152252 Hom.: 62011 Cov.: 32 AF XY: 0.905 AC XY: 67343 AN XY: 74446

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.889

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.891

Gnomad4 OTH AF: 0.897

Alfa AF: 0.895 Hom.: 7094

Bravo AF: 0.901

Asia WGS AF: 0.936 AC: 3253 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.84
DANN	Benign	0.79

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: rs4468527; hg19: chr14-52325131;