chr8-140824247-G-A

Variant names:

• chr8-140824247-G-A
• rs4551415
• NM_001352702.2:c.649-5227C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352702.2(PTK2):​c.649-5227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 152,268 control chromosomes in the GnomAD database, including 247 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 0.035 (247 hom., cov: 32)
• Consequence: PTK2 NM_001352702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 2 publications found

Genes affected

PTK2 (HGNC:9611): (protein tyrosine kinase 2) This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2	NM_001352702.2	c.649-5227C>T		intron_variant	Intron 8 of 35	ENST00000696786.1	NP_001339631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2	ENST00000696786.1	c.649-5227C>T		intron_variant	Intron 8 of 35		NM_001352702.2	ENSP00000512868.1

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5280 AN: 152150 Hom.: 247 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0721

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.00745

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0347 AC: 5291 AN: 152268 Hom.: 247 Cov.: 32 AF XY: 0.0352 AC XY: 2620 AN XY: 74448

African (AFR) AF: 0.101 AC: 4193 AN: 41542

American (AMR) AF: 0.0234 AC: 358 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.0717 AC: 372 AN: 5188

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4826

European-Finnish (FIN) AF: 0.00745 AC: 79 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00132 AC: 90 AN: 68032

Other (OTH) AF: 0.0260 AC: 55 AN: 2112

Alfa AF: 0.0128 Hom.: 14

Bravo AF: 0.0394

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.50
PhyloP100		0.11
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: rs4551415; hg19: chr8-141834346;