4-81201633-A-G

Position:

• chr4-81201633-A-G

Variant summary

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

The NM_006259.3(PRKG2):​c.461+2954T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,076 control chromosomes in the GnomAD database, including 18,241 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 0.42 (18241 hom., cov: 32)
• Consequence: PRKG2 NM_006259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

Genes affected

PRKG2 (HGNC:9416): (protein kinase cGMP-dependent 2) This gene encodes a protein that belongs to the serine/threonine protein kinase family of proteins. The encoded protein binds to and inhibits the activation of several receptor tyrosine kinases. The membrane-bound protein is a regulator of intestinal secretion, bone growth and renin secretion. Alternate splicing results in multiple transcript variants encoding distinct isoforms whose regulatory N-termini differ in length but whose C-terminal catalytic domains are identical. [provided by RefSeq, May 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG2	NM_006259.3	c.461+2954T>C		intron_variant		ENST00000264399.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG2	ENST00000264399.6	c.461+2954T>C		intron_variant		5	NM_006259.3	P1
PRKG2	ENST00000395578.3	c.461+2954T>C		intron_variant		5		P1
PRKG2	ENST00000628926.1	c.461+2954T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63024 AN: 151958 Hom.: 18194 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.415 AC: 63130 AN: 152076 Hom.: 18241 Cov.: 32 AF XY: 0.409 AC XY: 30437 AN XY: 74348

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.421

Alfa AF: 0.321 Hom.: 1506

Bravo AF: 0.454

Asia WGS AF: 0.450 AC: 1567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.4
DANN	Benign	0.55

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: rs10033237; hg19: chr4-82122787;