rs2302350

Variant names:

• chr12-6326587-G-A
• rs2302350
• NM_001384598.1:c.1670+14G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384598.1. 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
	PLEKHG6	NM_001384598.1	MANE Select	c.1670+14G>A		intron	N/A	NP_001371527.1	Q3KR16-1
	PLEKHG6	NM_001384604.1		c.1718+14G>A		intron	N/A	NP_001371533.1
	PLEKHG6	NM_001144856.2		c.1670+14G>A		intron	N/A	NP_001138328.1	A0A2X0TW08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHG6	ENST00000684764.1	MANE Select	c.1670+14G>A		intron	N/A	ENSP00000506982.1	Q3KR16-1
	PLEKHG6	ENST00000011684.11	TSL:1	c.1670+14G>A		intron	N/A	ENSP00000011684.7	Q3KR16-1
	PLEKHG6	ENST00000304581.8	TSL:1	c.260+14G>A		intron	N/A	ENSP00000304640.8	Q3KR16-3

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

GnomAD2 exomes AF: 0.407 AC: 54549 AN: 133974 AF XY: 0.415

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 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

African (AFR) AF: 0.0880 AC: 2334 AN: 26516

American (AMR) AF: 0.311 AC: 6973 AN: 22438

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 7386 AN: 18602

East Asian (EAS) AF: 0.224 AC: 7434 AN: 33220

South Asian (SAS) AF: 0.334 AC: 20704 AN: 61944

European-Finnish (FIN) AF: 0.574 AC: 26821 AN: 46750

Middle Eastern (MID) AF: 0.355 AC: 1794 AN: 5060

European-Non Finnish (NFE) AF: 0.482 AC: 497028 AN: 1031466

Other (OTH) AF: 0.416 AC: 21871 AN: 52586

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

African (AFR) AF: 0.100 AC: 4155 AN: 41508

American (AMR) AF: 0.344 AC: 5265 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1421 AN: 3472

East Asian (EAS) AF: 0.184 AC: 950 AN: 5156

South Asian (SAS) AF: 0.316 AC: 1518 AN: 4808

European-Finnish (FIN) AF: 0.586 AC: 6191 AN: 10572

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.484 AC: 32897 AN: 67966

Other (OTH) AF: 0.340 AC: 716 AN: 2108

Alfa AF: 0.369 Hom.: 5180

Bravo AF: 0.318

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.71
PhyloP100		-0.057
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: rs2302350; hg19: chr12-6435753; COSMIC: COSV50610025; COSMIC: COSV50610025;