8-27422364-C-T

Variant names:

• chr8-27422364-C-T
• rs112665817
• NM_173176.3:c.532C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_173176.3(PTK2B):​c.532C>T​(p.Leu178Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000915 in 1,613,210 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L178L) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0038 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00062 (6 hom.)
• Consequence: PTK2B NM_173176.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.77
• Publications: 0 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 8-27422364-C-T is Benign according to our data. Variant chr8-27422364-C-T is described in ClinVar as Benign. ClinVar VariationId is 792104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.77 with no splicing effect.
• BS2: High AC in GnomAd4 at 576 AD gene.

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.532C>T	p.Leu178Leu	synonymous	Exon 5 of 31	NP_775268.1	Q14289-1
	PTK2B	NM_004103.4		c.532C>T	p.Leu178Leu	synonymous	Exon 6 of 32	NP_004094.3	Q14289-1
	PTK2B	NM_173174.3		c.532C>T	p.Leu178Leu	synonymous	Exon 10 of 36	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.532C>T	p.Leu178Leu	synonymous	Exon 5 of 31	ENSP00000332816.6	Q14289-1
	PTK2B	ENST00000397501.5	TSL:1	c.532C>T	p.Leu178Leu	synonymous	Exon 10 of 36	ENSP00000380638.1	Q14289-1
	PTK2B	ENST00000894137.1		c.532C>T	p.Leu178Leu	synonymous	Exon 9 of 35	ENSP00000564196.1

Frequencies

GnomAD3 genomes AF: 0.00366 AC: 557 AN: 152266 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00133 AC: 330 AN: 248618 AF XY: 0.00126

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.000553

Gnomad ASJ exome AF: 0.000500

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000188

Gnomad OTH exome AF: 0.000987

GnomAD4 exome AF: 0.000616 AC: 900 AN: 1460826 Hom.: 6 Cov.: 30 AF XY: 0.000614 AC XY: 446 AN XY: 726716

African (AFR) AF: 0.0144 AC: 481 AN: 33462

American (AMR) AF: 0.000584 AC: 26 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.000920 AC: 24 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00233 AC: 201 AN: 86118

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53378

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5762

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1111448

Other (OTH) AF: 0.00152 AC: 92 AN: 60350

GnomAD4 genome AF: 0.00378 AC: 576 AN: 152384 Hom.: 5 Cov.: 33 AF XY: 0.00380 AC XY: 283 AN XY: 74520

African (AFR) AF: 0.0127 AC: 529 AN: 41598

American (AMR) AF: 0.00131 AC: 20 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68042

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00143 Hom.: 0

Bravo AF: 0.00389

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs112665817; hg19: chr8-27279881;