rs369083877

Variant names:

• chr1-44827577-C-G
• NM_003738.5:c.2196G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-44827577-C-G
• chr1-44827577-C-T

Variant summary

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

The NM_003738.5(PTCH2):​c.2196G>C​(p.Arg732Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R732T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTCH2 NM_003738.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCH2	NM_003738.5	c.2196G>C	p.Arg732Ser	missense_variant	Exon 15 of 22	ENST00000372192.4	NP_003729.3
PTCH2	NM_001166292.2	c.2196G>C	p.Arg732Ser	missense_variant	Exon 15 of 23		NP_001159764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCH2	ENST00000372192.4	c.2196G>C	p.Arg732Ser	missense_variant	Exon 15 of 22	1	NM_003738.5	ENSP00000361266.3
PTCH2	ENST00000447098.6	c.2196G>C	p.Arg732Ser	missense_variant	Exon 15 of 23	1		ENSP00000389703.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	.;D
Eigen	Benign	0.062
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	0.43	D
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.3	N;N
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.32	B;P
Vest4		0.34
MutPred		0.55		Loss of stability (P = 0.0923);Loss of stability (P = 0.0923);
MVP		0.93
MPC		0.21
ClinPred		0.96	D
GERP RS		4.1
Varity_R		0.38
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-45293249; COSMIC: COSV100942141; COSMIC: COSV100942141;