rs3779632

Variant names:

• chr8-27406593-T-C
• rs3779632
• NM_173176.3:c.204+8805T>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.204+8805T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,148 control chromosomes in the GnomAD database, including 53,543 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 0.83 (53543 hom., cov: 31)
• Consequence: PTK2B NM_173176.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173176.3. 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_173176.3	MANE Select	c.204+8805T>C		intron	N/A	NP_775268.1	Q14289-1
	PTK2B	NM_004103.4		c.204+8805T>C		intron	N/A	NP_004094.3	Q14289-1
	PTK2B	NM_173174.3		c.204+8805T>C		intron	N/A	NP_775266.1	Q14289-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK2B	ENST00000346049.10	TSL:1 MANE Select	c.204+8805T>C		intron	N/A	ENSP00000332816.6	Q14289-1
	PTK2B	ENST00000397501.5	TSL:1	c.204+8805T>C		intron	N/A	ENSP00000380638.1	Q14289-1
	PTK2B	ENST00000894137.1		c.204+8805T>C		intron	N/A	ENSP00000564196.1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126841 AN: 152030 Hom.: 53503 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.834 AC: 126937 AN: 152148 Hom.: 53543 Cov.: 31 AF XY: 0.828 AC XY: 61592 AN XY: 74378

African (AFR) AF: 0.882 AC: 36612 AN: 41504

American (AMR) AF: 0.721 AC: 11028 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3238 AN: 3472

East Asian (EAS) AF: 0.521 AC: 2686 AN: 5158

South Asian (SAS) AF: 0.860 AC: 4152 AN: 4826

European-Finnish (FIN) AF: 0.811 AC: 8587 AN: 10586

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57725 AN: 67996

Other (OTH) AF: 0.858 AC: 1813 AN: 2114

Alfa AF: 0.830 Hom.: 8553

Bravo AF: 0.828

Asia WGS AF: 0.719 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.29
PhyloP100		-0.61
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: rs3779632; hg19: chr8-27264110;