12-6326587-G-C

Variant names:

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

Variant summary

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

The NM_001384598.1(PLEKHG6):​c.1670+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,300,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.000015 (0 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: 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=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHG6	NM_001384598.1	c.1670+14G>C		intron_variant	Intron 14 of 15	ENST00000684764.1	NP_001371527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHG6	ENST00000684764.1	c.1670+14G>C		intron_variant	Intron 14 of 15		NM_001384598.1	ENSP00000506982.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000149 AC: 2 AN: 133974 AF XY: 0.0000272

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000302

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000146 AC: 19 AN: 1300024 Hom.: 0 Cov.: 32 AF XY: 0.00000940 AC XY: 6 AN XY: 638594

African (AFR) AF: 0.00 AC: 0 AN: 26528

American (AMR) AF: 0.00 AC: 0 AN: 22476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18628

East Asian (EAS) AF: 0.00 AC: 0 AN: 33236

South Asian (SAS) AF: 0.00 AC: 0 AN: 62086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5062

European-Non Finnish (NFE) AF: 0.0000184 AC: 19 AN: 1032550

Other (OTH) AF: 0.00 AC: 0 AN: 52648

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 5180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.69
PhyloP100		-0.057

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;