chr4-81148295-G-T

Variant names:

• chr4-81148295-G-T
• rs7688672
• NM_006259.3:c.1154+589C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006259.3(PRKG2):​c.1154+589C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PRKG2 NM_006259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 14 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006259.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG2	NM_006259.3	MANE Select	c.1154+589C>A		intron	N/A	NP_006250.1	Q13237-1
	PRKG2	NM_001363401.2		c.1154+589C>A		intron	N/A	NP_001350330.1	A0A140VJM3
	PRKG2	NM_001282485.2		c.1154+589C>A		intron	N/A	NP_001269414.1	Q13237-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG2	ENST00000264399.6	TSL:5 MANE Select	c.1154+589C>A		intron	N/A	ENSP00000264399.1	Q13237-1
	PRKG2	ENST00000945150.1		c.1277+589C>A		intron	N/A	ENSP00000615209.1
	PRKG2	ENST00000853043.1		c.1253+589C>A		intron	N/A	ENSP00000523102.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.21
PhyloP100		1.2

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: rs7688672; hg19: chr4-82069449;