8-140805075-A-G

Variant names:

• chr8-140805075-A-G
• rs9644448
• NM_001352702.2:c.868-1425T>C

Variant summary

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

The NM_001352702.2(PTK2):​c.868-1425T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,022 control chromosomes in the GnomAD database, including 2,632 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 0.17 (2632 hom., cov: 31)
• Consequence: PTK2 NM_001352702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK2	NM_001352702.2	MANE Select	c.868-1425T>C		intron	N/A	NP_001339631.1
	PTK2	NM_001352697.2		c.1000-1425T>C		intron	N/A	NP_001339626.1
	PTK2	NM_001387649.1		c.1000-1425T>C		intron	N/A	NP_001374578.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK2	ENST00000696786.1	MANE Select	c.868-1425T>C		intron	N/A	ENSP00000512868.1
	PTK2	ENST00000521059.5	TSL:1	c.868-1425T>C		intron	N/A	ENSP00000429474.1
	PTK2	ENST00000522684.5	TSL:1	c.868-1425T>C		intron	N/A	ENSP00000429911.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25909 AN: 151904 Hom.: 2633 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.171 AC: 25928 AN: 152022 Hom.: 2632 Cov.: 31 AF XY: 0.176 AC XY: 13063 AN XY: 74286

African (AFR) AF: 0.149 AC: 6196 AN: 41458

American (AMR) AF: 0.184 AC: 2812 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 235 AN: 3466

East Asian (EAS) AF: 0.477 AC: 2460 AN: 5152

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4816

European-Finnish (FIN) AF: 0.220 AC: 2322 AN: 10548

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10147 AN: 67984

Other (OTH) AF: 0.149 AC: 316 AN: 2114

Alfa AF: 0.167 Hom.: 379

Bravo AF: 0.169

Asia WGS AF: 0.336 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.80
DANN	Benign	0.44
PhyloP100		-0.37
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: rs9644448; hg19: chr8-141815174;