4-81092465-A-AAAGG

Position:

• chr4-81092465-A-AAAGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006259.3(PRKG2):​c.2127-14_2127-13insCCTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2517 hom., cov: 0)
  • Exomes 𝑓: 0.12 (6861 hom.)
• Consequence: PRKG2 NM_006259.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-81092465-A-AAAGG is Benign according to our data. Variant chr4-81092465-A-AAAGG is described in ClinVar as [Benign]. Clinvar id is 2798131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG2	NM_006259.3	c.2127-14_2127-13insCCTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000264399.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG2	ENST00000264399.6	c.2127-14_2127-13insCCTT		splice_polypyrimidine_tract_variant, intron_variant		5	NM_006259.3	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 22044 AN: 121580 Hom.: 2517 Cov.: 0

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.115 AC: 91611 AN: 793784 Hom.: 6861 Cov.: 16 AF XY: 0.120 AC XY: 48801 AN XY: 407724

Gnomad4 AFR exome AF: 0.0534

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.181 AC: 22055 AN: 121650 Hom.: 2517 Cov.: 0 AF XY: 0.180 AC XY: 10382 AN XY: 57644

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.202

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs59866145; hg19: chr4-82013619;