3-46519033-G-C

Variant names:

• chr3-46519033-G-C
• rs369355200
• NM_024512.5:c.1097C>G

Variant summary

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

The NM_024512.5(LRRC2):​c.1097C>G​(p.Ser366Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. S366Y) 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: 3.84
• Publications: 3 publications found

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

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=0.338378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.1097C>G	p.Ser366Cys	missense_variant	Exon 9 of 9	ENST00000395905.8	NP_078788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC2	ENST00000395905.8	c.1097C>G	p.Ser366Cys	missense_variant	Exon 9 of 9	1	NM_024512.5	ENSP00000379241.3
LRRC2	ENST00000296144.3	c.1097C>G	p.Ser366Cys	missense_variant	Exon 9 of 9	1		ENSP00000296144.3
LRRC2	ENST00000682605.1	c.1097C>G	p.Ser366Cys	missense_variant	Exon 9 of 9			ENSP00000507018.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251204 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M
PhyloP100		3.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;D
Vest4		0.38
MutPred		0.51		Loss of disorder (P = 6e-04);Loss of disorder (P = 6e-04);
MVP		0.38
MPC		0.87
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.18
gMVP		0.52
Mutation Taster		=79/21	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: rs369355200; hg19: chr3-46560523;