rs3639

Variant names:

• chr8-140674071-T-C
• rs3639
• NM_001352702.2:c.2832+227A>G

Variant summary

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

The NM_001352702.2(PTK2):​c.2832+227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 678,756 control chromosomes in the GnomAD database, including 31,281 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 0.28 (6360 hom., cov: 31)
  • Exomes 𝑓: 0.30 (24921 hom.)
• Consequence: PTK2 NM_001352702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2	NM_001352702.2	c.2832+227A>G		intron_variant	Intron 32 of 35	ENST00000696786.1	NP_001339631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2	ENST00000696786.1	c.2832+227A>G		intron_variant	Intron 32 of 35		NM_001352702.2	ENSP00000512868.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42371 AN: 151784 Hom.: 6350 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.298 AC: 157255 AN: 526854 Hom.: 24921 AF XY: 0.298 AC XY: 86278 AN XY: 289700

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.0856

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.279 AC: 42384 AN: 151902 Hom.: 6360 Cov.: 31 AF XY: 0.279 AC XY: 20732 AN XY: 74252

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.0845

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.266

Alfa AF: 0.313 Hom.: 1920

Bravo AF: 0.277

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.7
DANN	Benign	0.75

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: rs3639; hg19: chr8-141684170; COSMIC: COSV61781978; COSMIC: COSV61781978;