rs1553165053

Variant names:

• chr1-44827194-GT-AA
• rs1553165053
• NM_003738.5:c.2486_2487delACinsTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003738.5(PTCH2):​c.2486_2487delACinsTT​(p.Asp829Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.00000398 in 1 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. D829E) has been classified as Uncertain significance.

• Frequency: GnomAD MNV: 𝑓 0.0000040 Genomes: not found (cov: 33)
• Consequence: PTCH2 NM_003738.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.2486_2487delACinsTT	p.Asp829Val	missense	N/A	NP_003729.3
	PTCH2	NM_001166292.2		c.2486_2487delACinsTT	p.Asp829Val	missense	N/A	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.2486_2487delACinsTT	p.Asp829Val	missense	N/A	ENSP00000361266.3	Q9Y6C5-1
	PTCH2	ENST00000447098.7	TSL:1	c.2486_2487delACinsTT	p.Asp829Val	missense	N/A	ENSP00000389703.2	Q9Y6C5-2
	PTCH2	ENST00000881531.1		c.2435_2436delACinsTT	p.Asp812Val	missense	N/A	ENSP00000551590.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

GnomAD MNV AF: 0.00000398 AC: 1 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Gorlin syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

Splicing

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

Other links and lift over

dbSNP: rs1553165053; hg19: chr1-45292866;