rs11573587

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003738.5(PTCH2):c.2127C>T(p.Asp709Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,613,342 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 21 hom., cov: 33)

Exomes 𝑓: 0.019 ( 314 hom. )

Consequence

PTCH2
NM_003738.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.912

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 1-44827646-G-A is Benign according to our data. Variant chr1-44827646-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 415453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-44827646-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.912 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0142 (2158/152312) while in subpopulation NFE AF= 0.0232 (1578/68024). AF 95% confidence interval is 0.0222. There are 21 homozygotes in gnomad4. There are 1012 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCH2	NM_003738.5 linkuse as main transcript	c.2127C>T	p.Asp709Asp	synonymous_variant	15/22	ENST00000372192.4	NP_003729.3	Q9Y6C5-1
PTCH2	NM_001166292.2 linkuse as main transcript	c.2127C>T	p.Asp709Asp	synonymous_variant	15/23		NP_001159764.1	Q9Y6C5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCH2	ENST00000372192.4 linkuse as main transcript	c.2127C>T	p.Asp709Asp	synonymous_variant	15/22	1	NM_003738.5	ENSP00000361266.3		Q9Y6C5-1
PTCH2	ENST00000447098.6 linkuse as main transcript	c.2127C>T	p.Asp709Asp	synonymous_variant	15/23	1		ENSP00000389703.2		Q9Y6C5-2

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2158

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0232

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0134

AC:

3324

AN:

248898

Hom.:

AF XY:

0.0138

AC XY:

1854

AN XY:

134776

show subpopulations

Gnomad AFR exome

AF:

0.00303

Gnomad AMR exome

AF:

0.00868

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00601

Gnomad FIN exome

AF:

0.00703

Gnomad NFE exome

AF:

0.0206

Gnomad OTH exome

AF:

0.0139

GnomAD4 exome

AF:

0.0186

AC:

27180

AN:

1461030

Hom.:

314

Cov.:

AF XY:

0.0184

AC XY:

13340

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.00877

Gnomad4 ASJ exome

AF:

0.0279

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00588

Gnomad4 FIN exome

AF:

0.00709

Gnomad4 NFE exome

AF:

0.0217

Gnomad4 OTH exome

AF:

0.0165

GnomAD4 genome

AF:

0.0142

AC:

2158

AN:

152312

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1012

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00390

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00600

Gnomad4 FIN

AF:

0.00659

Gnomad4 NFE

AF:

0.0232

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0179

Hom.:

Bravo

AF:

0.0135

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 01, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Basal cell carcinoma, susceptibility to, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Gorlin syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.5

DANN

Benign

0.87

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

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