chr8-140674071-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.386 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.2832+227A>G		intron	N/A	NP_001339631.1
	PTK2	NM_001352697.2		c.2901+227A>G		intron	N/A	NP_001339626.1
	PTK2	NM_001387649.1		c.2880+227A>G		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.2832+227A>G		intron	N/A	ENSP00000512868.1
	PTK2	ENST00000521059.5	TSL:1	c.2709+227A>G		intron	N/A	ENSP00000429474.1
	PTK2	ENST00000522684.5	TSL:1	c.2709+227A>G		intron	N/A	ENSP00000429911.1

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

African (AFR) AF: 0.196 AC: 3120 AN: 15928

American (AMR) AF: 0.406 AC: 16067 AN: 39596

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 6379 AN: 18340

East Asian (EAS) AF: 0.0856 AC: 2535 AN: 29618

South Asian (SAS) AF: 0.282 AC: 18672 AN: 66250

European-Finnish (FIN) AF: 0.311 AC: 8951 AN: 28808

Middle Eastern (MID) AF: 0.314 AC: 1173 AN: 3736

European-Non Finnish (NFE) AF: 0.311 AC: 92110 AN: 296482

Other (OTH) AF: 0.294 AC: 8248 AN: 28096

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

African (AFR) AF: 0.198 AC: 8222 AN: 41434

American (AMR) AF: 0.394 AC: 6012 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3466

East Asian (EAS) AF: 0.0845 AC: 436 AN: 5158

South Asian (SAS) AF: 0.270 AC: 1301 AN: 4818

European-Finnish (FIN) AF: 0.292 AC: 3070 AN: 10524

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21290 AN: 67954

Other (OTH) AF: 0.266 AC: 562 AN: 2110

Alfa AF: 0.309 Hom.: 2946

Bravo AF: 0.277

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.7
DANN	Benign	0.75
PhyloP100		-0.11
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: rs3639; hg19: chr8-141684170; COSMIC: COSV61781978; COSMIC: COSV61781978;