NM_024512.5:c.126-2551T>A

Variant names:

• chr3-46547804-A-T
• rs9808967
• NM_024512.5:c.126-2551T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024512.5(LRRC2):​c.126-2551T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,096 control chromosomes in the GnomAD database, including 575 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 0.080 (575 hom., cov: 32)
• Consequence: LRRC2 NM_024512.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 6 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]

LRRC2-AS1 (HGNC:15571): (LRRC2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC2	NM_024512.5	c.126-2551T>A		intron_variant	Intron 2 of 8	ENST00000395905.8	NP_078788.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC2	ENST00000395905.8	c.126-2551T>A		intron_variant	Intron 2 of 8	1	NM_024512.5	ENSP00000379241.3

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12219 AN: 151978 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0385

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0788

Gnomad OTH AF: 0.0689

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

GnomAD4 genome AF: 0.0805 AC: 12243 AN: 152096 Hom.: 575 Cov.: 32 AF XY: 0.0851 AC XY: 6327 AN XY: 74340

African (AFR) AF: 0.0698 AC: 2898 AN: 41512

American (AMR) AF: 0.0384 AC: 586 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3470

East Asian (EAS) AF: 0.0924 AC: 479 AN: 5184

South Asian (SAS) AF: 0.170 AC: 817 AN: 4820

European-Finnish (FIN) AF: 0.154 AC: 1620 AN: 10548

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.0788 AC: 5356 AN: 67978

Other (OTH) AF: 0.0687 AC: 145 AN: 2112

Alfa AF: 0.0821 Hom.: 62

Bravo AF: 0.0710

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.69
DANN	Benign	0.66
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

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: rs9808967; hg19: chr3-46589294;