4-81092465-A-AAAGGAAGG

Position:

• chr4-81092465-A-AAAGGAAGG

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_2127-13insCCTTCCTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6445 hom., cov: 0)
  • Exomes 𝑓: 0.18 (24008 hom.)
• Consequence: PRKG2 NM_006259.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely 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-AAAGGAAGG is Benign according to our data. Variant chr4-81092465-A-AAAGGAAGG is described in ClinVar as [Likely_benign]. Clinvar id is 2975970.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKG2	NM_006259.3	c.2127-14_2127-13insCCTTCCTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000264399.6	NP_006250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKG2	ENST00000264399.6	c.2127-14_2127-13insCCTTCCTT		splice_polypyrimidine_tract_variant, intron_variant		5	NM_006259.3	ENSP00000264399	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 35705 AN: 121524 Hom.: 6440 Cov.: 0

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.183 AC: 146228 AN: 800470 Hom.: 24008 Cov.: 16 AF XY: 0.189 AC XY: 77742 AN XY: 411148

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.556

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.294 AC: 35728 AN: 121592 Hom.: 6445 Cov.: 0 AF XY: 0.303 AC XY: 17429 AN XY: 57610

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.297

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 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;