8-140955682-G-T

Variant names:

• chr8-140955682-G-T
• rs1375062
• NM_001352702.2:c.-121-29933C>A

Variant summary

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

The NM_001352702.2(PTK2):​c.-121-29933C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,924 control chromosomes in the GnomAD database, including 15,172 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 0.42 (15172 hom., cov: 32)
• Consequence: PTK2 NM_001352702.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 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.-121-29933C>A		intron	N/A	NP_001339631.1	A0A8Q3WLM4
	PTK2	NM_001352697.2		c.-309+28396C>A		intron	N/A	NP_001339626.1
	PTK2	NM_001387649.1		c.-407-29933C>A		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.-121-29933C>A		intron	N/A	ENSP00000512868.1	A0A8Q3WLM4
	PTK2	ENST00000521059.5	TSL:1	c.-33+28396C>A		intron	N/A	ENSP00000429474.1	Q05397-1
	PTK2	ENST00000522684.5	TSL:1	c.-121-29933C>A		intron	N/A	ENSP00000429911.1	Q05397-1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63451 AN: 151804 Hom.: 15163 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.418 AC: 63480 AN: 151924 Hom.: 15172 Cov.: 32 AF XY: 0.414 AC XY: 30739 AN XY: 74258

African (AFR) AF: 0.187 AC: 7737 AN: 41438

American (AMR) AF: 0.377 AC: 5750 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2187 AN: 3464

East Asian (EAS) AF: 0.379 AC: 1955 AN: 5162

South Asian (SAS) AF: 0.427 AC: 2053 AN: 4808

European-Finnish (FIN) AF: 0.460 AC: 4844 AN: 10538

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.547 AC: 37186 AN: 67944

Other (OTH) AF: 0.491 AC: 1035 AN: 2108

Alfa AF: 0.495 Hom.: 9145

Bravo AF: 0.405

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		-0.17
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: rs1375062; hg19: chr8-141965781;