rs11705987

Positions:

• chr3-46542582-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024512.5(LRRC2):​c.333+2464T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,734 control chromosomes in the GnomAD database, including 3,839 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3839 hom., cov: 31)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.333+2464T>G		intron_variant		ENST00000395905.8	NP_078788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC2	ENST00000395905.8	c.333+2464T>G		intron_variant		1	NM_024512.5	ENSP00000379241	P1
LRRC2	ENST00000296144.3	c.333+2464T>G		intron_variant		1		ENSP00000296144	P1
LRRC2	ENST00000682605.1	c.333+2464T>G		intron_variant				ENSP00000507018	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31294 AN: 151616 Hom.: 3838 Cov.: 31

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31305 AN: 151734 Hom.: 3839 Cov.: 31 AF XY: 0.209 AC XY: 15454 AN XY: 74114

Gnomad4 AFR AF: 0.0587

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.236

Alfa AF: 0.233 Hom.: 774

Bravo AF: 0.191

Asia WGS AF: 0.225 AC: 780 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.53

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: rs11705987; hg19: chr3-46584072;