13-48707149-G-C

Variant names:

• chr13-48707149-G-C
• NM_001308476.3:c.332G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001308476.3(CYSLTR2):​c.332G>C​(p.Cys111Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYSLTR2 NM_001308476.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.84

Genes affected

CYSLTR2 (HGNC:18274): (cysteinyl leukotriene receptor 2) The cysteinyl leukotrienes LTC4, LTD4, and LTE4 are important mediators of human bronchial asthma. Pharmacologic studies have determined that cysteinyl leukotrienes activate at least 2 receptors, the protein encoded by this gene and CYSLTR1. This encoded receptor is a member of the superfamily of G protein-coupled receptors. It seems to play a major role in endocrine and cardiovascular systems. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYSLTR2	NM_001308476.3	c.332G>C	p.Cys111Ser	missense_variant	Exon 5 of 5	ENST00000682523.1	NP_001295405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYSLTR2	ENST00000682523.1	c.332G>C	p.Cys111Ser	missense_variant	Exon 5 of 5		NM_001308476.3	ENSP00000508181.1
CYSLTR2	ENST00000614739.4	c.332G>C	p.Cys111Ser	missense_variant	Exon 5 of 5	1		ENSP00000477930.1
CYSLTR2	ENST00000282018.4	c.332G>C	p.Cys111Ser	missense_variant	Exon 1 of 1	6		ENSP00000282018.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.332G>C (p.C111S) alteration is located in exon 1 (coding exon 1) of the CYSLTR2 gene. This alteration results from a G to C substitution at nucleotide position 332, causing the cysteine (C) at amino acid position 111 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D;D
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.74	.;T
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Pathogenic	4.3	H;H
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-9.8	.;D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.91
MutPred		0.70		Gain of catalytic residue at R112 (P = 0);Gain of catalytic residue at R112 (P = 0);
MVP		0.88
MPC		0.64
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.98
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr13-49281285;