rs28834970

Positions:

• chr8-27337604-T-C

Variant summary

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

The NM_173176.3(PTK2B):​c.-38+11923T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,126 control chromosomes in the GnomAD database, including 8,173 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 0.32 (8173 hom., cov: 33)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.-38+11923T>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.-38+11923T>C		intron_variant		1	NM_173176.3	ENSP00000332816	A1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48371 AN: 152006 Hom.: 8160 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.318 AC: 48410 AN: 152126 Hom.: 8173 Cov.: 33 AF XY: 0.321 AC XY: 23900 AN XY: 74354

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.342

Alfa AF: 0.316 Hom.: 990

Bravo AF: 0.302

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.66

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: rs28834970; hg19: chr8-27195121;