chr8-27385557-C-T

Position:

• chr8-27385557-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.-37-11991C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,148 control chromosomes in the GnomAD database, including 1,435 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 0.12 (1435 hom., cov: 31)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK2B	NM_173176.3	c.-37-11991C>T		intron_variant		ENST00000346049.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK2B	ENST00000346049.10	c.-37-11991C>T		intron_variant		1	NM_173176.3	A1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18164 AN: 152030 Hom.: 1434 Cov.: 31

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.0747

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.0950

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

GnomAD4 genome AF: 0.119 AC: 18159 AN: 152148 Hom.: 1435 Cov.: 31 AF XY: 0.116 AC XY: 8639 AN XY: 74380

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.0746

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.0950

Alfa AF: 0.155 Hom.: 2627

Bravo AF: 0.111

Asia WGS AF: 0.146 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.19
DANN	Benign	0.58

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: rs17057065; hg19: chr8-27243074;