NM_173176.3:c.50G>T

Variant names:

• chr8-27397634-G-T
• rs145156050
• NM_173176.3:c.50G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173176.3(PTK2B):​c.50G>T​(p.Arg17Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PTK2B NM_173176.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2875114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK2B	NM_173176.3	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 31	ENST00000346049.10	NP_775268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK2B	ENST00000346049.10	c.50G>T	p.Arg17Leu	missense_variant	Exon 2 of 31	1	NM_173176.3	ENSP00000332816.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;.;T;.;T;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.0091
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	.;T;T;T;T;T;T;.
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.29	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.8	L;.;.;L;L;.;.;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	N;D;D;N;N;N;N;N
REVEL	Benign	0.28
Sift	Uncertain	0.0040	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.021	D;D;D;D;D;D;D;D
Polyphen		0.012	B;.;.;B;B;.;.;B
Vest4		0.47
MutPred		0.51		Loss of MoRF binding (P = 0.0132);Loss of MoRF binding (P = 0.0132);Loss of MoRF binding (P = 0.0132);Loss of MoRF binding (P = 0.0132);Loss of MoRF binding (P = 0.0132);Loss of MoRF binding (P = 0.0132);Loss of MoRF binding (P = 0.0132);Loss of MoRF binding (P = 0.0132);
MVP		0.81
MPC		0.42
ClinPred		0.75	D
GERP RS		3.9
Varity_R		0.095
gMVP		0.26

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: rs145156050; hg19: chr8-27255151;