rs10109834

Positions:

• chr8-27354759-A-C
• chr8-27354759-A-G
• chr8-27354759-A-T

Variant summary

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

The ENST00000346049.10(PTK2B):​c.-38+29078A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,982 control chromosomes in the GnomAD database, including 14,883 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 0.44 (14883 hom., cov: 31)
• Consequence: PTK2B ENST00000346049.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.-38+29078A>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+29078A>C		intron_variant		1	NM_173176.3	ENSP00000332816	A1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66232 AN: 151864 Hom.: 14874 Cov.: 31

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.436 AC: 66278 AN: 151982 Hom.: 14883 Cov.: 31 AF XY: 0.426 AC XY: 31619 AN XY: 74274

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.444

Alfa AF: 0.469 Hom.: 22852

Bravo AF: 0.440

Asia WGS AF: 0.215 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.34

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: rs10109834; hg19: chr8-27212276;