8-27362470-C-T

Position:

• chr8-27362470-C-T

Variant summary

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

The NM_173176.3(PTK2B):​c.-37-35078C>T 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 152,020 control chromosomes in the GnomAD database, including 8,158 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 (8158 hom., cov: 31)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.-37-35078C>T		intron_variant		ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.-37-35078C>T		intron_variant		1	NM_173176.3	ENSP00000332816.6

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48305 AN: 151902 Hom.: 8146 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.318 AC: 48343 AN: 152020 Hom.: 8158 Cov.: 31 AF XY: 0.321 AC XY: 23873 AN XY: 74314

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.342

Alfa AF: 0.192 Hom.: 419

Bravo AF: 0.302

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.49

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: rs73223431; hg19: chr8-27219987;