rs10496163

Positions:

• chr2-68381295-A-G
• chr2-68381295-A-T

Variant summary

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

The NM_002664.3(PLEK):​c.380+391A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 152,306 control chromosomes in the GnomAD database, including 69 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 0.023 (69 hom., cov: 32)
• Consequence: PLEK NM_002664.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

Genes affected

PLEK (HGNC:9070): (pleckstrin) Enables phosphatidylinositol-3,4-bisphosphate binding activity; protein homodimerization activity; and protein kinase C binding activity. Involved in several processes, including G protein-coupled receptor signaling pathway; actin cytoskeleton organization; and positive regulation of supramolecular fiber organization. Located in cytoplasm and ruffle membrane. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEK	NM_002664.3	c.380+391A>G		intron_variant		ENST00000234313.8
PLEK	XM_047444772.1	c.380+391A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEK	ENST00000234313.8	c.380+391A>G		intron_variant		1	NM_002664.3	P1

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3536 AN: 152188 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0249

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0232 AC: 3534 AN: 152306 Hom.: 69 Cov.: 32 AF XY: 0.0243 AC XY: 1809 AN XY: 74468

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.0689

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.0274

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0143 Hom.: 7

Bravo AF: 0.0274

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.091
DANN	Benign	0.78

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: rs10496163; hg19: chr2-68608427;