NM_002821.5:c.962-3C>T

Variant names:

• chr6-43132418-C-T
• rs141307288
• NM_002821.5:c.962-3C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The NM_002821.5(PTK7):​c.962-3C>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00766 in 1,565,650 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (52 hom.)
• Consequence: PTK7 NM_002821.5 splice_region, intron
• Scores: Splicing: ADA: 0.8248
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.95
• Publications: 2 publications found

Genes affected

PTK7 (HGNC:9618): (protein tyrosine kinase 7 (inactive)) This gene encodes a member of the receptor protein tyrosine kinase family of proteins that transduce extracellular signals across the cell membrane. The encoded protein lacks detectable catalytic tyrosine kinase activity, is involved in the Wnt signaling pathway and plays a role in multiple cellular processes including polarity and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 6-43132418-C-T is Benign according to our data. Variant chr6-43132418-C-T is described in ClinVar as Benign. ClinVar VariationId is 773328.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 762 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002821.5. 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
	PTK7	NM_002821.5	MANE Select	c.962-3C>T		splice_region intron	N/A	NP_002812.2
	PTK7	NM_001270398.2		c.986-3C>T		splice_region intron	N/A	NP_001257327.1	Q13308-6
	PTK7	NM_152880.4		c.962-3C>T		splice_region intron	N/A	NP_690619.1	Q13308-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK7	ENST00000230419.9	TSL:1 MANE Select	c.962-3C>T		splice_region intron	N/A	ENSP00000230419.4	Q13308-1
	PTK7	ENST00000345201.6	TSL:1	c.962-3C>T		splice_region intron	N/A	ENSP00000325992.4	Q13308-2
	PTK7	ENST00000352931.6	TSL:1	c.962-3C>T		splice_region intron	N/A	ENSP00000326029.3	Q13308-4

Frequencies

GnomAD3 genomes AF: 0.00501 AC: 763 AN: 152176 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00877

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00418 AC: 922 AN: 220644 AF XY: 0.00421

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.00140

Gnomad ASJ exome AF: 0.00495

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00747

Gnomad OTH exome AF: 0.00527

GnomAD4 exome AF: 0.00795 AC: 11230 AN: 1413356 Hom.: 52 Cov.: 31 AF XY: 0.00761 AC XY: 5296 AN XY: 695742

African (AFR) AF: 0.00122 AC: 40 AN: 32694

American (AMR) AF: 0.00152 AC: 63 AN: 41474

Ashkenazi Jewish (ASJ) AF: 0.00546 AC: 125 AN: 22908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39072

South Asian (SAS) AF: 0.000644 AC: 51 AN: 79244

European-Finnish (FIN) AF: 0.00188 AC: 97 AN: 51634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 0.00968 AC: 10478 AN: 1082534

Other (OTH) AF: 0.00645 AC: 376 AN: 58264

GnomAD4 genome AF: 0.00500 AC: 762 AN: 152294 Hom.: 5 Cov.: 32 AF XY: 0.00450 AC XY: 335 AN XY: 74452

African (AFR) AF: 0.00142 AC: 59 AN: 41556

American (AMR) AF: 0.00438 AC: 67 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00878 AC: 597 AN: 68030

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00602 Hom.: 3

Bravo AF: 0.00490

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.97
PhyloP100		6.9
PromoterAI		0.0098	Neutral
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.82
dbscSNV1_RF	Benign	0.43
SpliceAI score (max)		0.17		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: rs141307288; hg19: chr6-43100156; COSMIC: COSV57849220;