rs201560633

Variant names:

• chr3-46521558-C-G
• rs201560633
• NM_024512.5:c.1030G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-46521558-C-G
• chr3-46521558-C-T

Variant summary

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

The NM_024512.5(LRRC2):​c.1030G>C​(p.Val344Leu) 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. 14/21 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. V344I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC2 NM_024512.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64

Genes affected

LRRC2 (HGNC:14676): (leucine rich repeat containing 2) This gene encodes a member of the leucine-rich repeat-containing family of proteins, which function in diverse biological pathways. This family member may possibly be a nuclear protein. Similarity to the RAS suppressor protein, as well as expression down-regulation observed in tumor cells, suggests that it may function as a tumor suppressor. The gene is located in the chromosome 3 common eliminated region 1 (C3CER1), a 1.4 Mb region that is commonly deleted in diverse tumors. A related pseudogene has been identified on chromosome 2. [provided by RefSeq, Sep 2011]

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=0.077782065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.1030G>C	p.Val344Leu	missense_variant	Exon 8 of 9	ENST00000395905.8	NP_078788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC2	ENST00000395905.8	c.1030G>C	p.Val344Leu	missense_variant	Exon 8 of 9	1	NM_024512.5	ENSP00000379241.3
LRRC2	ENST00000296144.3	c.1030G>C	p.Val344Leu	missense_variant	Exon 8 of 9	1		ENSP00000296144.3
LRRC2	ENST00000682605.1	c.1030G>C	p.Val344Leu	missense_variant	Exon 8 of 9			ENSP00000507018.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0016	T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.37	N;N
REVEL	Benign	0.016
Sift	Uncertain	0.027	D;D
Sift4G	Benign	0.34	T;T
Polyphen		0.0010	B;B
Vest4		0.20
MutPred		0.28		Gain of glycosylation at Y348 (P = 0.0349);Gain of glycosylation at Y348 (P = 0.0349);
MVP		0.067
MPC		0.26
ClinPred		0.35	T
GERP RS		2.2
Varity_R		0.064
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs201560633; hg19: chr3-46563048;