2-68371823-T-C

Position:

• chr2-68371823-T-C

Variant summary

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

The NM_002664.3(PLEK):​c.42+6430T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,868 control chromosomes in the GnomAD database, including 10,038 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 (10038 hom., cov: 31)
• Consequence: PLEK NM_002664.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEK	NM_002664.3	c.42+6430T>C		intron_variant		ENST00000234313.8	NP_002655.2
PLEK	XM_047444772.1	c.42+6430T>C		intron_variant			XP_047300728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEK	ENST00000234313.8	c.42+6430T>C		intron_variant		1	NM_002664.3	ENSP00000234313.7

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52414 AN: 151750 Hom.: 10027 Cov.: 31

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.345 AC: 52462 AN: 151868 Hom.: 10038 Cov.: 31 AF XY: 0.352 AC XY: 26132 AN XY: 74222

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.358

Alfa AF: 0.311 Hom.: 17303

Bravo AF: 0.365

Asia WGS AF: 0.575 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.48

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: rs17035378; hg19: chr2-68598955;