Variant chr3-46521579-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024512.5(LRRC2):c.1009C>T(p.Arg337Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000556 in 1,612,658 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 3 hom. )

Consequence

LRRC2
NM_024512.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.55

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006883949).

BP6

Variant 3-46521579-G-A is Benign according to our data. Variant chr3-46521579-G-A is described in ClinVar as [Benign]. Clinvar id is 785049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC2	NM_024512.5 link	c.1009C>T	p.Arg337Cys	missense_variant	8/9	ENST00000395905.8	NP_078788.2	Q9BYS8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC2	ENST00000395905.8 link	c.1009C>T	p.Arg337Cys	missense_variant	8/9	1	NM_024512.5	ENSP00000379241.3	Q9BYS8
LRRC2	ENST00000296144.3 link	c.1009C>T	p.Arg337Cys	missense_variant	8/9	1		ENSP00000296144.3	Q9BYS8
LRRC2	ENST00000682605.1 link	c.1009C>T	p.Arg337Cys	missense_variant	8/9			ENSP00000507018.1	Q9BYS8

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

428

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000984

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000790

AC:

198

AN:

250716

Hom.:

AF XY:

0.000546

AC XY:

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.000609

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000319

AC:

466

AN:

1460482

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

210

AN XY:

726652

show subpopulations

Gnomad4 AFR exome

AF:

0.00929

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00283

AC:

431

AN:

152176

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00978

Gnomad4 AMR

AF:

0.000983

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000551

Hom.:

Bravo

AF:

0.00352

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00101

AC:

122

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

.;D

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

1.0

D;D

Vest4

0.70

MVP

0.43

MPC

1.0

ClinPred

0.036

GERP RS

4.6

Varity_R

0.14

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over