chr4-81160834-T-C

Variant names:

• chr4-81160834-T-C
• rs6828114
• NM_006259.3:c.912+6327A>G

Variant summary

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

The NM_006259.3(PRKG2):​c.912+6327A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,066 control chromosomes in the GnomAD database, including 4,733 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 0.19 (4733 hom., cov: 32)
• Consequence: PRKG2 NM_006259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKG2	NM_006259.3	c.912+6327A>G		intron_variant	Intron 6 of 18	ENST00000264399.6	NP_006250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG2	ENST00000264399.6	c.912+6327A>G		intron_variant	Intron 6 of 18	5	NM_006259.3	ENSP00000264399.1
PRKG2	ENST00000395578.3	c.912+6327A>G		intron_variant	Intron 6 of 18	5		ENSP00000378945.1
PRKG2	ENST00000628926.1	c.912+6327A>G		intron_variant	Intron 6 of 18	2		ENSP00000486129.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28483 AN: 151948 Hom.: 4720 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.188 AC: 28535 AN: 152066 Hom.: 4733 Cov.: 32 AF XY: 0.189 AC XY: 14016 AN XY: 74352

African (AFR) AF: 0.417 AC: 17265 AN: 41424

American (AMR) AF: 0.150 AC: 2288 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2380 AN: 5170

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4818

European-Finnish (FIN) AF: 0.0588 AC: 623 AN: 10596

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0602 AC: 4091 AN: 67998

Other (OTH) AF: 0.174 AC: 368 AN: 2116

Alfa AF: 0.138 Hom.: 380

Bravo AF: 0.208

Asia WGS AF: 0.320 AC: 1111 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.4
DANN	Benign	0.69
PhyloP100		1.0
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: rs6828114; hg19: chr4-82081988;