chr8-140658761-A-T

Variant names:

• chr8-140658761-A-T
• rs7460
• ENST00000519993.5:n.*3544T>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000519993.5(PTK2):​n.*3544T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 221,350 control chromosomes in the GnomAD database, including 20,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12839 hom., cov: 32)
  • Exomes 𝑓: 0.46 (7675 hom.)
• Consequence: PTK2 ENST00000519993.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.831
• Publications: 29 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 8-140658761-A-T is Benign according to our data. Variant chr8-140658761-A-T is described in ClinVar as Benign. ClinVar VariationId is 1226102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2	NM_001352702.2	c.*705T>A		3_prime_UTR_variant	Exon 36 of 36	ENST00000696786.1	NP_001339631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2	ENST00000696786.1	c.*705T>A		3_prime_UTR_variant	Exon 36 of 36		NM_001352702.2	ENSP00000512868.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59043 AN: 151950 Hom.: 12828 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.460 AC: 31872 AN: 69282 Hom.: 7675 Cov.: 0 AF XY: 0.469 AC XY: 15027 AN XY: 32052

African (AFR) AF: 0.182 AC: 593 AN: 3254

American (AMR) AF: 0.423 AC: 892 AN: 2108

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 2316 AN: 4362

East Asian (EAS) AF: 0.353 AC: 3507 AN: 9942

South Asian (SAS) AF: 0.390 AC: 234 AN: 600

European-Finnish (FIN) AF: 0.424 AC: 162 AN: 382

Middle Eastern (MID) AF: 0.510 AC: 213 AN: 418

European-Non Finnish (NFE) AF: 0.501 AC: 21292 AN: 42474

Other (OTH) AF: 0.464 AC: 2663 AN: 5742

GnomAD4 genome AF: 0.388 AC: 59065 AN: 152068 Hom.: 12839 Cov.: 32 AF XY: 0.388 AC XY: 28812 AN XY: 74314

African (AFR) AF: 0.181 AC: 7518 AN: 41512

American (AMR) AF: 0.392 AC: 5980 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1877 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1899 AN: 5180

South Asian (SAS) AF: 0.433 AC: 2084 AN: 4814

European-Finnish (FIN) AF: 0.437 AC: 4615 AN: 10550

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33477 AN: 67962

Other (OTH) AF: 0.457 AC: 964 AN: 2108

Alfa AF: 0.302 Hom.: 880

Bravo AF: 0.379

Asia WGS AF: 0.392 AC: 1367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24930376)

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.8
DANN	Benign	0.80
PhyloP100		0.83
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: rs7460; hg19: chr8-141668860;