Variant 3-46521635-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024512.5(LRRC2):c.953C>T(p.Pro318Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00131 in 1,612,594 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 18 hom. )

Consequence

LRRC2
NM_024512.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.79

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067184865).

BP6

Variant 3-46521635-G-A is Benign according to our data. Variant chr3-46521635-G-A is described in ClinVar as [Benign]. Clinvar id is 708653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00648 (987/152258) while in subpopulation AFR AF= 0.0221 (920/41538). AF 95% confidence interval is 0.021. There are 13 homozygotes in gnomad4. There are 472 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC2	NM_024512.5 linkuse as main transcript	c.953C>T	p.Pro318Leu	missense_variant	8/9	ENST00000395905.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRRC2	ENST00000395905.8 linkuse as main transcript	c.953C>T	p.Pro318Leu	missense_variant	8/9	1	NM_024512.5	P1
LRRC2	ENST00000296144.3 linkuse as main transcript	c.953C>T	p.Pro318Leu	missense_variant	8/9	1		P1
LRRC2	ENST00000682605.1 linkuse as main transcript	c.953C>T	p.Pro318Leu	missense_variant	8/9			P1

Frequencies

GnomAD3 genomes

AF:

0.00642

AC:

977

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00171

AC:

427

AN:

250344

Hom.:

AF XY:

0.00122

AC XY:

165

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000770

AC:

1124

AN:

1460336

Hom.:

Cov.:

AF XY:

0.000652

AC XY:

474

AN XY:

726520

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.00193

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.00648

AC:

987

AN:

152258

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

472

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.00771

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00210

AC:

255

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 10, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.000075

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

.;T

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.14

T;T

Polyphen

0.0030

B;B

Vest4

0.70

MVP

0.27

MPC

0.93

ClinPred

0.11

GERP RS

3.5

Varity_R

0.53

gMVP

0.56

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