NM_001352702.2:c.195+4388C>T

Variant names:

• chr8-140886155-G-A
• rs1868280
• NM_001352702.2:c.195+4388C>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.195+4388C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,994 control chromosomes in the GnomAD database, including 14,728 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 0.41 (14728 hom., cov: 31)
• Consequence: PTK2 NM_001352702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352702.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK2	NM_001352702.2	MANE Select	c.195+4388C>T		intron	N/A	NP_001339631.1	A0A8Q3WLM4
	PTK2	NM_001352697.2		c.327+4388C>T		intron	N/A	NP_001339626.1
	PTK2	NM_001387649.1		c.327+4388C>T		intron	N/A	NP_001374578.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK2	ENST00000696786.1	MANE Select	c.195+4388C>T		intron	N/A	ENSP00000512868.1	A0A8Q3WLM4
	PTK2	ENST00000521059.5	TSL:1	c.195+4388C>T		intron	N/A	ENSP00000429474.1	Q05397-1
	PTK2	ENST00000522684.5	TSL:1	c.195+4388C>T		intron	N/A	ENSP00000429911.1	Q05397-1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62461 AN: 151876 Hom.: 14718 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.411 AC: 62489 AN: 151994 Hom.: 14728 Cov.: 31 AF XY: 0.408 AC XY: 30279 AN XY: 74276

African (AFR) AF: 0.184 AC: 7611 AN: 41458

American (AMR) AF: 0.366 AC: 5591 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2129 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1851 AN: 5168

South Asian (SAS) AF: 0.427 AC: 2058 AN: 4824

European-Finnish (FIN) AF: 0.455 AC: 4796 AN: 10538

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

European-Non Finnish (NFE) AF: 0.541 AC: 36762 AN: 67952

Other (OTH) AF: 0.482 AC: 1016 AN: 2110

Alfa AF: 0.512 Hom.: 27402

Bravo AF: 0.398

Asia WGS AF: 0.391 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.76
PhyloP100		0.18
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: rs1868280; hg19: chr8-141896254;