8-27313969-T-C

Variant names:

• chr8-27313969-T-C
• rs7833348
• ENST00000397501.5:c.-414+682T>C

Variant summary

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

The NM_173174.3(PTK2B):​c.-414+682T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 152,312 control chromosomes in the GnomAD database, including 71,815 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 0.97 (71815 hom., cov: 31)
• Consequence: PTK2B NM_173174.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980
• Publications: 5 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173174.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK2B	NM_173174.3		c.-414+682T>C		intron	N/A	NP_775266.1	Q14289-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK2B	ENST00000397501.5	TSL:1	c.-414+682T>C		intron	N/A	ENSP00000380638.1	Q14289-1
	PTK2B	ENST00000894137.1		c.-254+682T>C		intron	N/A	ENSP00000564196.1
	PTK2B	ENST00000894138.1		c.-254+2260T>C		intron	N/A	ENSP00000564197.1

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147756 AN: 152194 Hom.: 71756 Cov.: 31

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.981

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.962

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

GnomAD4 genome AF: 0.971 AC: 147874 AN: 152312 Hom.: 71815 Cov.: 31 AF XY: 0.972 AC XY: 72422 AN XY: 74474

African (AFR) AF: 0.991 AC: 41203 AN: 41558

American (AMR) AF: 0.962 AC: 14728 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 3340 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5177 AN: 5178

South Asian (SAS) AF: 0.987 AC: 4759 AN: 4824

European-Finnish (FIN) AF: 0.981 AC: 10419 AN: 10620

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.956 AC: 65047 AN: 68030

Other (OTH) AF: 0.963 AC: 2037 AN: 2116

Alfa AF: 0.958 Hom.: 83740

Bravo AF: 0.970

Asia WGS AF: 0.992 AC: 3452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.47
PhyloP100		-0.98
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: rs7833348; hg19: chr8-27171486;