chr1-44822461-C-T

Position:

• chr1-44822461-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000372192.4(PTCH2):​c.3566G>A​(p.Ser1189Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1189T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTCH2 ENST00000372192.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071959764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCH2	NM_003738.5	c.3566G>A	p.Ser1189Asn	missense_variant	22/22	ENST00000372192.4	NP_003729.3
PTCH2	NM_001166292.2	c.3425+141G>A		intron_variant			NP_001159764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCH2	ENST00000372192.4	c.3566G>A	p.Ser1189Asn	missense_variant	22/22	1	NM_003738.5	ENSP00000361266	P2
PTCH2	ENST00000447098.6	c.3425+141G>A		intron_variant		1		ENSP00000389703	A2
PTCH2	ENST00000438067.5	c.186+141G>A		intron_variant		3		ENSP00000413169

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.76
DANN	Benign	0.81
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.33	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.22
Sift	Benign	0.14	T
Sift4G	Benign	0.42	T
Polyphen		0.0030	B
Vest4		0.040
MutPred		0.095		Loss of glycosylation at S1189 (P = 0.0034);
MVP		0.70
MPC		0.16
ClinPred		0.095	T
GERP RS		1.4
Varity_R		0.053
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-45288133;