4-81193349-C-T

Position:

• chr4-81193349-C-T

Variant summary

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

The NM_006259.3(PRKG2):​c.461+11238G>A 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 152,038 control chromosomes in the GnomAD database, including 18,430 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 (18430 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PRKG2 NM_006259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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]

PRKG2-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKG2	NM_006259.3	c.461+11238G>A		intron_variant		ENST00000264399.6	NP_006250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKG2	ENST00000264399.6	c.461+11238G>A		intron_variant		5	NM_006259.3	ENSP00000264399.1
PRKG2	ENST00000395578.3	c.461+11238G>A		intron_variant		5		ENSP00000378945.1
PRKG2	ENST00000628926.1	c.461+11238G>A		intron_variant		2		ENSP00000486129.1
PRKG2-AS1	ENST00000512502.5	n.736C>T		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63041 AN: 151916 Hom.: 18385 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.415 AC: 63139 AN: 152034 Hom.: 18430 Cov.: 32 AF XY: 0.408 AC XY: 30349 AN XY: 74328

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.409

Alfa AF: 0.271 Hom.: 12805

Bravo AF: 0.451

Asia WGS AF: 0.439 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3733553; hg19: chr4-82114503;