14-51899056-A-G

Variant names:

• chr14-51899056-A-G
• rs1316298
• NM_053064.5:c.-30+21399A>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+21399A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,060 control chromosomes in the GnomAD database, including 9,746 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 0.35 (9746 hom., cov: 32)
• Consequence: GNG2 NM_053064.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 8 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 (SAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053064.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNG2	NM_053064.5	MANE Select	c.-30+21399A>G		intron	N/A	NP_444292.1
	GNG2	NM_001243773.2		c.-30+21399A>G		intron	N/A	NP_001230702.1
	GNG2	NM_001243774.2		c.-30+38266A>G		intron	N/A	NP_001230703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNG2	ENST00000556766.6	TSL:1 MANE Select	c.-30+21399A>G		intron	N/A	ENSP00000451231.1
	GNG2	ENST00000556752.2	TSL:1	c.-30+21399A>G		intron	N/A	ENSP00000451576.1
	GNG2	ENST00000553299.5	TSL:1	n.387+21399A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53671 AN: 151942 Hom.: 9749 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.353 AC: 53687 AN: 152060 Hom.: 9746 Cov.: 32 AF XY: 0.351 AC XY: 26127 AN XY: 74330

African (AFR) AF: 0.299 AC: 12391 AN: 41484

American (AMR) AF: 0.341 AC: 5221 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1423 AN: 5176

South Asian (SAS) AF: 0.433 AC: 2084 AN: 4812

European-Finnish (FIN) AF: 0.358 AC: 3784 AN: 10566

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26165 AN: 67946

Other (OTH) AF: 0.348 AC: 735 AN: 2112

Alfa AF: 0.367 Hom.: 14919

Bravo AF: 0.350

Asia WGS AF: 0.347 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.2
DANN	Benign	0.89
PhyloP100		-0.057
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: rs1316298; hg19: chr14-52365774;