rs10033237

Variant names:

• chr4-81201633-A-G
• rs10033237
• NM_006259.3:c.461+2954T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.97).
• 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 rank	MANE	Protein	UniProt
PRKG2	NM_006259.3	c.461+2954T>C		intron_variant	Intron 2 of 18	ENST00000264399.6	NP_006250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKG2	ENST00000264399.6	c.461+2954T>C		intron_variant	Intron 2 of 18	5	NM_006259.3	ENSP00000264399.1
PRKG2	ENST00000395578.3	c.461+2954T>C		intron_variant	Intron 2 of 18	5		ENSP00000378945.1
PRKG2	ENST00000628926.1	c.461+2954T>C		intron_variant	Intron 2 of 18	2		ENSP00000486129.1

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

African (AFR) AF: 0.809 AC: 33571 AN: 41474

American (AMR) AF: 0.379 AC: 5790 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1275 AN: 3472

East Asian (EAS) AF: 0.475 AC: 2458 AN: 5176

South Asian (SAS) AF: 0.387 AC: 1865 AN: 4816

European-Finnish (FIN) AF: 0.127 AC: 1343 AN: 10592

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15528 AN: 67964

Other (OTH) AF: 0.421 AC: 889 AN: 2112

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
PhyloP100		0.22
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: rs10033237; hg19: chr4-82122787;