rs1012003418

Variant names:

• chr13-48707122-C-A
• rs1012003418
• NM_001308476.3:c.305C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-48707122-C-A
• chr13-48707122-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001308476.3(CYSLTR2):​c.305C>A​(p.Ser102Tyr) 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. 13/22 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. S102F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYSLTR2 NM_001308476.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3110754).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308476.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR2	NM_001308476.3	MANE Select	c.305C>A	p.Ser102Tyr	missense	Exon 5 of 5	NP_001295405.1	Q9NS75
	CYSLTR2	NM_001308465.3		c.305C>A	p.Ser102Tyr	missense	Exon 6 of 6	NP_001295394.1	Q9NS75
	CYSLTR2	NM_001308467.3		c.305C>A	p.Ser102Tyr	missense	Exon 6 of 6	NP_001295396.1	Q9NS75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYSLTR2	ENST00000682523.1	MANE Select	c.305C>A	p.Ser102Tyr	missense	Exon 5 of 5	ENSP00000508181.1	Q9NS75
	CYSLTR2	ENST00000614739.4	TSL:1	c.305C>A	p.Ser102Tyr	missense	Exon 5 of 5	ENSP00000477930.1	Q9NS75
	CYSLTR2	ENST00000282018.4	TSL:6	c.305C>A	p.Ser102Tyr	missense	Exon 1 of 1	ENSP00000282018.3	Q9NS75

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.2
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.16
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.033	D
Polyphen		0.12	B
Vest4		0.56
MutPred		0.60		Gain of catalytic residue at N103 (P = 0.0028)
MVP		0.64
MPC		0.65
ClinPred		0.94	D
GERP RS		4.3
Varity_R		0.38
gMVP		0.042
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1012003418; hg19: chr13-49281258;