rs7827965

Positions:

• chr8-27430516-T-C
• chr8-27430516-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173176.3(PTK2B):​c.669+98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,502,362 control chromosomes in the GnomAD database, including 159,916 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 0.46 (15972 hom., cov: 31)
  • Exomes 𝑓: 0.46 (143944 hom.)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

Genes affected

PTK2B (HGNC:9612): (protein tyrosine kinase 2 beta) This gene encodes a cytoplasmic protein tyrosine kinase which is involved in calcium-induced regulation of ion channels and activation of the map kinase signaling pathway. The encoded protein may represent an important signaling intermediate between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity. The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration, nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation. This protein has been shown to bind CRK-associated substrate, nephrocystin, GTPase regulator associated with FAK, and the SH2 domain of GRB2. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.669+98T>C		intron_variant		ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.669+98T>C		intron_variant		1	NM_173176.3	ENSP00000332816	A1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69103 AN: 151660 Hom.: 15960 Cov.: 31

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.457 AC: 617707 AN: 1350584 Hom.: 143944 AF XY: 0.460 AC XY: 310856 AN XY: 675868

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.414

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.578

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.456 AC: 69136 AN: 151778 Hom.: 15972 Cov.: 31 AF XY: 0.453 AC XY: 33600 AN XY: 74136

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.443

Alfa AF: 0.448 Hom.: 15703

Bravo AF: 0.455

Asia WGS AF: 0.451 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.39

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: rs7827965; hg19: chr8-27288033; COSMIC: COSV57758158; COSMIC: COSV57758158;