1-44827254-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000372192.4(PTCH2):c.2427G>C(p.Ser809Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,614,134 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S809S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.011 ( 19 hom., cov: 33)

Exomes 𝑓: 0.013 ( 166 hom. )

Consequence

PTCH2
ENST00000372192.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.17

Publications

3 publications found

Variant links:

COSMIC-nc: COSV104679503

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 Gene-Disease associations (from GenCC):

nevoid basal cell carcinoma syndrome
Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
commissural facial cleft
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PTCH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-44827254-C-G is Benign according to our data. Variant chr1-44827254-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 239557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0112 (1705/152314) while in subpopulation NFE AF = 0.0185 (1257/68008). AF 95% confidence interval is 0.0176. There are 19 homozygotes in GnomAd4. There are 818 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1705 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000372192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCH2	NM_003738.5	MANE Select	c.2427G>C	p.Ser809Ser	synonymous	Exon 16 of 22	NP_003729.3
	PTCH2	NM_001166292.2		c.2427G>C	p.Ser809Ser	synonymous	Exon 16 of 23	NP_001159764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCH2	ENST00000372192.4	TSL:1 MANE Select	c.2427G>C	p.Ser809Ser	synonymous	Exon 16 of 22	ENSP00000361266.3
	PTCH2	ENST00000447098.7	TSL:1	c.2427G>C	p.Ser809Ser	synonymous	Exon 16 of 23	ENSP00000389703.2

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1705

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0191

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0185

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.0119

AC:

2986

AN:

251368

AF XY:

0.0120

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00804

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0182

Gnomad NFE exome

AF:

0.0174

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0130

AC:

19044

AN:

1461820

Hom.:

166

Cov.:

AF XY:

0.0129

AC XY:

9396

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00182

AC:

AN:

33480

American (AMR)

AF:

0.00865

AC:

387

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

344

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00233

AC:

201

AN:

86258

European-Finnish (FIN)

AF:

0.0188

AC:

1001

AN:

53350

Middle Eastern (MID)

AF:

0.0144

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0146

AC:

16280

AN:

1112008

Other (OTH)

AF:

0.0114

AC:

686

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1386

2772

4159

5545

6931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

536

1072

1608

2144

2680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0112

AC:

1705

AN:

152314

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

818

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00166

AC:

AN:

41582

American (AMR)

AF:

0.00712

AC:

109

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00310

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0191

AC:

203

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0185

AC:

1257

AN:

68008

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

178

268

357

446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0130

Hom.:

Bravo

AF:

0.00977

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0170

EpiControl

AF:

0.0176

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Basal cell carcinoma, susceptibility to, 1 (1)

Basal cell nevus syndrome 1 (1)

Gorlin syndrome (1)

PTCH2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.16

(source)

DANN

Benign

0.70

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over