rs2302350

Positions:

• chr12-6326587-G-A
• chr12-6326587-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384598.1(PLEKHG6):​c.1670+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,450,664 control chromosomes in the GnomAD database, including 151,579 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 0.35 (11773 hom., cov: 31)
  • Exomes 𝑓: 0.46 (139806 hom.)
• Consequence: PLEKHG6 NM_001384598.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

Genes affected

PLEKHG6 (HGNC:25562): (pleckstrin homology and RhoGEF domain containing G6) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in cell junction and centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG6	NM_001384598.1	c.1670+14G>A		intron_variant		ENST00000684764.1	NP_001371527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHG6	ENST00000684764.1	c.1670+14G>A		intron_variant			NM_001384598.1	ENSP00000506982	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53583 AN: 151964 Hom.: 11775 Cov.: 31

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.338

GnomAD3 exomes AF: 0.407 AC: 54549 AN: 133974 Hom.: 11911 AF XY: 0.415 AC XY: 30514 AN XY: 73596

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.402

Gnomad EAS exome AF: 0.190

Gnomad SAS exome AF: 0.324

Gnomad FIN exome AF: 0.569

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.456 AC: 592345 AN: 1298582 Hom.: 139806 Cov.: 32 AF XY: 0.455 AC XY: 289966 AN XY: 637886

Gnomad4 AFR exome AF: 0.0880

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.397

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.574

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.352 AC: 53586 AN: 152082 Hom.: 11773 Cov.: 31 AF XY: 0.357 AC XY: 26538 AN XY: 74320

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.340

Alfa AF: 0.359 Hom.: 3103

Bravo AF: 0.318

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs2302350; hg19: chr12-6435753; COSMIC: COSV50610025; COSMIC: COSV50610025;