8-27445498-T-C

Variant names:

• chr8-27445498-T-C
• rs11135993
• NM_173176.3:c.2215-296T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173176.3(PTK2B):​c.2215-296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,000 control chromosomes in the GnomAD database, including 15,692 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 0.45 (15692 hom., cov: 32)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.2215-296T>C		intron_variant	Intron 23 of 30	ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.2215-296T>C		intron_variant	Intron 23 of 30	1	NM_173176.3	ENSP00000332816.6

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68410 AN: 151882 Hom.: 15676 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.450 AC: 68440 AN: 152000 Hom.: 15692 Cov.: 32 AF XY: 0.447 AC XY: 33242 AN XY: 74284

African (AFR) AF: 0.483 AC: 20037 AN: 41456

American (AMR) AF: 0.420 AC: 6410 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1229 AN: 5166

South Asian (SAS) AF: 0.540 AC: 2597 AN: 4812

European-Finnish (FIN) AF: 0.425 AC: 4492 AN: 10572

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30763 AN: 67938

Other (OTH) AF: 0.442 AC: 930 AN: 2106

Alfa AF: 0.446 Hom.: 25808

Bravo AF: 0.450

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.50
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11135993; hg19: chr8-27303015;