chr1-44821874-A-C

Variant names:

• chr1-44821874-A-C
• rs147018154
• ENST00000447098.7:c.3425+728T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000447098.7(PTCH2):​c.3425+728T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000824 in 1,213,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: PTCH2 ENST00000447098.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• 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: 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

LOC107984952 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.04).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107984952	XR_001738036.3	n.728A>C		non_coding_transcript_exon_variant	Exon 2 of 2
PTCH2	NM_001166292.2	c.3425+728T>G		intron_variant	Intron 22 of 22		NP_001159764.1
PTCH2	NM_003738.5	c.*541T>G		downstream_gene_variant		ENST00000372192.4	NP_003729.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCH2	ENST00000447098.7	c.3425+728T>G		intron_variant	Intron 22 of 22	1		ENSP00000389703.2
PTCH2	ENST00000438067.5	c.216T>G	p.Tyr72*	stop_gained	Exon 4 of 5	3		ENSP00000413169.1
PTCH2	ENST00000372192.4	c.*541T>G		downstream_gene_variant		1	NM_003738.5	ENSP00000361266.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.24e-7 AC: 1 AN: 1213472 Hom.: 0 Cov.: 31 AF XY: 0.00000166 AC XY: 1 AN XY: 601266

African (AFR) AF: 0.00 AC: 0 AN: 26276

American (AMR) AF: 0.00 AC: 0 AN: 37202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16866

East Asian (EAS) AF: 0.00 AC: 0 AN: 16812

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4476

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 953576

Other (OTH) AF: 0.00 AC: 0 AN: 43976

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.86
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs147018154; hg19: chr1-45287546;