1-44821874-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000447098.6(PTCH2):c.3425+728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,365,722 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (19 hom.)
• Consequence: PTCH2 ENST00000447098.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.194

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]

LOC107984952 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-44821874-A-G is Benign according to our data. Variant chr1-44821874-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 686 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107984952	XR_001738036.3	n.728A>G		non_coding_transcript_exon_variant	2/2
PTCH2	NM_001166292.2	c.3425+728T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTCH2	ENST00000447098.6	c.3425+728T>C		intron_variant		1		A2
PTCH2	ENST00000438067.5	c.219T>C	p.Tyr73=	synonymous_variant	4/5	3

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 686 AN: 152156 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00665

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00430 AC: 1030 AN: 239512 Hom.: 6 AF XY: 0.00430 AC XY: 566 AN XY: 131518

Gnomad AFR exome AF: 0.000784

Gnomad AMR exome AF: 0.00222

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000368

Gnomad FIN exome AF: 0.0118

Gnomad NFE exome AF: 0.00612

Gnomad OTH exome AF: 0.00455

GnomAD4 exome AF: 0.00623 AC: 7564 AN: 1213448 Hom.: 19 Cov.: 31 AF XY: 0.00598 AC XY: 3597 AN XY: 601250

Gnomad4 AFR exome AF: 0.000875

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.000178

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000495

Gnomad4 FIN exome AF: 0.0128

Gnomad4 NFE exome AF: 0.00712

Gnomad4 OTH exome AF: 0.00514

GnomAD4 genome AF: 0.00451 AC: 687 AN: 152274 Hom.: 3 Cov.: 32 AF XY: 0.00438 AC XY: 326 AN XY: 74452

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00561 Hom.: 1

Bravo AF: 0.00353

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

PTCH2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.58
Dann	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147018154; hg19: chr1-45287546;