3-46539186-A-C

Variant names:

• chr3-46539186-A-C
• rs34850909
• NM_024512.5:c.349T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024512.5(LRRC2):​c.349T>G​(p.Leu117Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L117M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC2 NM_024512.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024512.5. 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
	LRRC2	NM_024512.5	MANE Select	c.349T>G	p.Leu117Val	missense	Exon 4 of 9	NP_078788.2	Q9BYS8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC2	ENST00000395905.8	TSL:1 MANE Select	c.349T>G	p.Leu117Val	missense	Exon 4 of 9	ENSP00000379241.3	Q9BYS8
	LRRC2	ENST00000296144.3	TSL:1	c.349T>G	p.Leu117Val	missense	Exon 4 of 9	ENSP00000296144.3	Q9BYS8
	LRRC2	ENST00000872818.1		c.460T>G	p.Leu154Val	missense	Exon 4 of 9	ENSP00000542877.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		-0.14
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.042	D
Polyphen		0.99	D
Vest4		0.73
MutPred		0.44		Gain of methylation at K118 (P = 0.0379)
MVP		0.23
MPC		0.92
ClinPred		0.98	D
GERP RS		-3.4
Varity_R		0.38
gMVP		0.53
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs34850909; hg19: chr3-46580676;