rs11573579

Variant names:

• chr1-44829617-C-A
• rs11573579
• NM_003738.5:c.1080G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-44829617-C-A
• chr1-44829617-C-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_003738.5(PTCH2):​c.1080G>T​(p.Val360Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0088 in 1,614,206 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V360V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0062 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0091 (70 hom.)
• Consequence: PTCH2 NM_003738.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.00300
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-44829617-C-A is Benign according to our data. Variant chr1-44829617-C-A is described in ClinVar as Benign. ClinVar VariationId is 239553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.003 with no splicing effect.
• BS2: High AC in GnomAd4 at 950 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.1080G>T	p.Val360Val	synonymous	Exon 8 of 22	NP_003729.3
	PTCH2	NM_001166292.2		c.1080G>T	p.Val360Val	synonymous	Exon 8 of 23	NP_001159764.1	Q9Y6C5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCH2	ENST00000372192.4	TSL:1 MANE Select	c.1080G>T	p.Val360Val	synonymous	Exon 8 of 22	ENSP00000361266.3	Q9Y6C5-1
	PTCH2	ENST00000447098.7	TSL:1	c.1080G>T	p.Val360Val	synonymous	Exon 8 of 23	ENSP00000389703.2	Q9Y6C5-2
	PTCH2	ENST00000881531.1		c.1029G>T	p.Val343Val	synonymous	Exon 8 of 22	ENSP00000551590.1

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 950 AN: 152212 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00613 AC: 1540 AN: 251366 AF XY: 0.00631

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0127

Gnomad NFE exome AF: 0.00926

Gnomad OTH exome AF: 0.00961

GnomAD4 exome AF: 0.00906 AC: 13250 AN: 1461876 Hom.: 70 Cov.: 32 AF XY: 0.00899 AC XY: 6538 AN XY: 727240

African (AFR) AF: 0.00125 AC: 42 AN: 33480

American (AMR) AF: 0.00293 AC: 131 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00149 AC: 39 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00110 AC: 95 AN: 86258

European-Finnish (FIN) AF: 0.0110 AC: 588 AN: 53402

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.0107 AC: 11885 AN: 1112012

Other (OTH) AF: 0.00737 AC: 445 AN: 60396

GnomAD4 genome AF: 0.00624 AC: 950 AN: 152330 Hom.: 9 Cov.: 33 AF XY: 0.00611 AC XY: 455 AN XY: 74488

African (AFR) AF: 0.00185 AC: 77 AN: 41560

American (AMR) AF: 0.00242 AC: 37 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.0108 AC: 115 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0103 AC: 702 AN: 68034

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00737 Hom.: 5

Bravo AF: 0.00533

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0117

EpiControl AF: 0.00907

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Basal cell carcinoma, susceptibility to, 1 (1)
-	-	1	Basal cell nevus syndrome 1 (1)
-	-	1	Gorlin syndrome (1)
-	-	1	not specified (1)
-	-	1	PTCH2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	5.6
DANN	Benign	0.74
PhyloP100		0.0030
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11573579; hg19: chr1-45295289;