rs10496163

Variant names:

• chr2-68381295-A-G
• rs10496163
• NM_002664.3:c.380+391A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLEK	NM_002664.3	c.380+391A>G		intron_variant	Intron 3 of 8	ENST00000234313.8	NP_002655.2
PLEK	XM_047444772.1	c.380+391A>G		intron_variant	Intron 3 of 7		XP_047300728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEK	ENST00000234313.8	c.380+391A>G		intron_variant	Intron 3 of 8	1	NM_002664.3	ENSP00000234313.7

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

African (AFR) AF: 0.0268 AC: 1112 AN: 41568

American (AMR) AF: 0.0689 AC: 1054 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.0274 AC: 142 AN: 5184

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4822

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10618

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 876 AN: 68022

Other (OTH) AF: 0.0241 AC: 51 AN: 2114

Alfa AF: 0.0145 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
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism

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: rs10496163; hg19: chr2-68608427;