dbSNP rs45573433: PTCH2:p.Leu30Leu (chr1-44842022-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_003738.5(PTCH2):c.90G>A(p.Leu30Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,006 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 10 hom., cov: 32)

Exomes 𝑓: 0.012 ( 117 hom. )

Consequence

PTCH2
NM_003738.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.686

Variant links:

Genes affected

PTCH2 (HGNC:9586): (patched 2) This gene encodes a transmembrane receptor of the patched gene family. The encoded protein may function as a tumor suppressor in the hedgehog signaling pathway. Alterations in this gene have been associated with nevoid basal cell carcinoma syndrome, basal cell carcinoma, medulloblastoma, and susceptibility to congenital macrostomia. Alternatively spliced transcript variants have been described.[provided by RefSeq, Oct 2009]

PTCH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 1-44842022-C-T is Benign according to our data. Variant chr1-44842022-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 239563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-44842022-C-T is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 1400 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCH2	NM_003738.5 link	c.90G>A	p.Leu30Leu	synonymous_variant	Exon 2 of 22	ENST00000372192.4	NP_003729.3	Q9Y6C5-1
PTCH2	NM_001166292.2 link	c.90G>A	p.Leu30Leu	synonymous_variant	Exon 2 of 23		NP_001159764.1	Q9Y6C5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCH2	ENST00000372192.4 link	c.90G>A	p.Leu30Leu	synonymous_variant	Exon 2 of 22	1	NM_003738.5	ENSP00000361266.3		Q9Y6C5-1
PTCH2	ENST00000447098.6 link	c.90G>A	p.Leu30Leu	synonymous_variant	Exon 2 of 23	1		ENSP00000389703.2		Q9Y6C5-2

Frequencies

GnomAD3 genomes

AF:

0.00920

AC:

1400

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0297

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0101

AC:

2530

AN:

251390

Hom.:

AF XY:

0.0103

AC XY:

1396

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.00413

Gnomad ASJ exome

AF:

0.00982

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.0316

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0120

AC:

17557

AN:

1460672

Hom.:

117

Cov.:

AF XY:

0.0118

AC XY:

8546

AN XY:

726712

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00454

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00290

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.00975

GnomAD4 genome

AF:

0.00919

AC:

1400

AN:

152334

Hom.:

Cov.:

AF XY:

0.00995

AC XY:

741

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00253

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0297

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.00738

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0135

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 14, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PTCH2: BS1, BS2 -

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Basal cell carcinoma, susceptibility to, 1

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Gorlin syndrome

Benign:1

Jan 18, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Basal cell nevus syndrome 1

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: -34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over