1-44842914-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003738.5(PTCH2):c.19C>G(p.Leu7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,548,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L7F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

PTCH2
NM_003738.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.87

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

nevoid basal cell carcinoma syndrome
Inheritance: Unknown, AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp
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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11557928).

BS2

High AC in GnomAdExome4 at 52 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003738.5. 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
	PTCH2	NM_003738.5	MANE Select	c.19C>G	p.Leu7Val	missense	Exon 1 of 22	NP_003729.3
	PTCH2	NM_001166292.2		c.19C>G	p.Leu7Val	missense	Exon 1 of 23	NP_001159764.1	Q9Y6C5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTCH2	ENST00000372192.4	TSL:1 MANE Select	c.19C>G	p.Leu7Val	missense	Exon 1 of 22	ENSP00000361266.3	Q9Y6C5-1
PTCH2	ENST00000447098.7	TSL:1	c.19C>G	p.Leu7Val	missense	Exon 1 of 23	ENSP00000389703.2	Q9Y6C5-2
PTCH2	ENST00000881531.1		c.19C>G	p.Leu7Val	missense	Exon 1 of 22	ENSP00000551590.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

150160

AF XY:

0.0000126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000838

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000174

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000372

AC:

AN:

1396776

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

688914

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31406

American (AMR)

AF:

0.0000847

AC:

AN:

35424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25104

East Asian (EAS)

AF:

0.00

AC:

AN:

35554

South Asian (SAS)

AF:

0.00

AC:

AN:

78852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.0000445

AC:

AN:

1077970

Other (OTH)

AF:

0.0000173

AC:

AN:

57896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Gorlin syndrome (1)

Gorlin syndrome;C0025149:Medulloblastoma;C2751544:Basal cell carcinoma, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.095

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.65

M_CAP

Benign

0.063

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.69

PhyloP100

2.9

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.24

REVEL

Benign

0.25

Sift

Benign

0.033

Sift4G

Benign

0.31

Polyphen

0.14

Vest4

0.087

MutPred

0.11

Gain of glycosylation at S4 (P = 0.0868)

MVP

0.87

MPC

0.19

ClinPred

0.19

GERP RS

3.8

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.16

gMVP

0.47

Mutation Taster

=95/5

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

Computational scores

Splicing

Publications

Other links and lift over