chr13-48707139-G-T

Position:

• chr13-48707139-G-T

Variant summary

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

The NM_001308476.3(CYSLTR2):​c.322G>T​(p.Asp108Tyr) variant causes a missense change. 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: 6.82

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, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYSLTR2	NM_001308476.3	c.322G>T	p.Asp108Tyr	missense_variant	5/5	ENST00000682523.1	NP_001295405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYSLTR2	ENST00000682523.1	c.322G>T	p.Asp108Tyr	missense_variant	5/5		NM_001308476.3	ENSP00000508181.1
CYSLTR2	ENST00000614739.4	c.322G>T	p.Asp108Tyr	missense_variant	5/5	1		ENSP00000477930.1
CYSLTR2	ENST00000282018.4	c.322G>T	p.Asp108Tyr	missense_variant	1/1	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.322G>T (p.D108Y) alteration is located in exon 1 (coding exon 1) of the CYSLTR2 gene. This alteration results from a G to T substitution at nucleotide position 322, causing the aspartic acid (D) at amino acid position 108 to be replaced by a tyrosine (Y). 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	0.62
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.4	.;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;D
Vest4		0.90
MutPred		0.65		Gain of catalytic residue at R112 (P = 0);Gain of catalytic residue at R112 (P = 0);
MVP		0.92
MPC		0.63
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.80
gMVP		0.31

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: chr13-49281275;