8-140706149-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001352702.2(PTK2):c.2322A>C(p.Pro774=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,613,092 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (7 hom.)
• Consequence: PTK2 NM_001352702.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.18

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-140706149-T-G is Benign according to our data. Variant chr8-140706149-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 709439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.18 with no splicing effect.
• BS2: High AC in GnomAd at 183 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2	NM_001352702.2	c.2322A>C	p.Pro774=	synonymous_variant	27/36	ENST00000696786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2	ENST00000696786.1	c.2322A>C	p.Pro774=	synonymous_variant	27/36		NM_001352702.2	P4

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 183 AN: 152236 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00115 AC: 289 AN: 251438 Hom.: 2 AF XY: 0.00104 AC XY: 141 AN XY: 135898

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00160

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00200 AC: 2923 AN: 1460738 Hom.: 7 Cov.: 30 AF XY: 0.00192 AC XY: 1395 AN XY: 726772

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.000957

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.000187

Gnomad4 NFE exome AF: 0.00241

Gnomad4 OTH exome AF: 0.00194

GnomAD4 genome AF: 0.00120 AC: 183 AN: 152354 Hom.: 1 Cov.: 33 AF XY: 0.00110 AC XY: 82 AN XY: 74498

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00197

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00140 Hom.: 0

Bravo AF: 0.00122

EpiCase AF: 0.00126

EpiControl AF: 0.00124

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.14
Dann	Benign	0.73

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: rs147531538; hg19: chr8-141716248;