4-81141777-C-T

Variant names:

• chr4-81141777-C-T
• rs6837293
• NM_006259.3:c.1407+1017G>A

Variant summary

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

The NM_006259.3(PRKG2):​c.1407+1017G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,308 control chromosomes in the GnomAD database, including 16,826 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 0.38 (16826 hom., cov: 32)
• Consequence: PRKG2 NM_006259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• acromesomelic dysplasia 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG2	NM_006259.3	c.1407+1017G>A		intron_variant	Intron 11 of 18	ENST00000264399.6	NP_006250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG2	ENST00000264399.6	c.1407+1017G>A		intron_variant	Intron 11 of 18	5	NM_006259.3	ENSP00000264399.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57750 AN: 151188 Hom.: 16772 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.382 AC: 57859 AN: 151308 Hom.: 16826 Cov.: 32 AF XY: 0.379 AC XY: 28016 AN XY: 73974

African (AFR) AF: 0.808 AC: 33063 AN: 40936

American (AMR) AF: 0.302 AC: 4582 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1152 AN: 3460

East Asian (EAS) AF: 0.558 AC: 2880 AN: 5162

South Asian (SAS) AF: 0.385 AC: 1854 AN: 4812

European-Finnish (FIN) AF: 0.101 AC: 1072 AN: 10566

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12196 AN: 67912

Other (OTH) AF: 0.379 AC: 792 AN: 2090

Alfa AF: 0.231 Hom.: 13985

Bravo AF: 0.416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.54
PhyloP100		0.71
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: rs6837293; hg19: chr4-82062931;