rs12097

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002294.3(LAMP2):c.156A>T(p.Val52Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,146,848 control chromosomes in the GnomAD database, including 69,015 homozygotes. There are 144,907 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 6245 hom., 12724 hem., cov: 22)

Exomes 𝑓: 0.41 ( 62770 hom. 132183 hem. )

Consequence

LAMP2
NM_002294.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

LAMP2 (HGNC:6501): (lysosomal associated membrane protein 2) The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may play a role in tumor cell metastasis. It may also function in the protection, maintenance, and adhesion of the lysosome. Alternative splicing of this gene results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

LAMP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-120456678-T-A is Benign according to our data. Variant chrX-120456678-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 44416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-120456678-T-A is described in Lovd as [Benign]. Variant chrX-120456678-T-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3 link	c.156A>T	p.Val52Val	synonymous_variant	Exon 2 of 9	ENST00000200639.9	NP_002285.1	P13473-1
LAMP2	NM_001122606.1 link	c.156A>T	p.Val52Val	synonymous_variant	Exon 2 of 9		NP_001116078.1	P13473-3
LAMP2	NM_013995.2 link	c.156A>T	p.Val52Val	synonymous_variant	Exon 2 of 9		NP_054701.1	P13473-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMP2	ENST00000200639.9 link	c.156A>T	p.Val52Val	synonymous_variant	Exon 2 of 9	1	NM_002294.3	ENSP00000200639.4	P13473-1
LAMP2	ENST00000434600.6 link	c.156A>T	p.Val52Val	synonymous_variant	Exon 2 of 9	1		ENSP00000408411.2	P13473-3
LAMP2	ENST00000371335.4 link	c.156A>T	p.Val52Val	synonymous_variant	Exon 2 of 9	1		ENSP00000360386.4	P13473-2
LAMP2	ENST00000706600.1 link	c.156A>T	p.Val52Val	synonymous_variant	Exon 2 of 9			ENSP00000516464.1	A0A9L9PXQ4

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

43545

AN:

110486

Hom.:

6253

Cov.:

AF XY:

0.387

AC XY:

12685

AN XY:

32760

show subpopulations

Gnomad AFR

AF:

0.348

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.485

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.374

GnomAD3 exomes

AF:

0.390

AC:

66801

AN:

171407

Hom.:

9060

AF XY:

0.379

AC XY:

21867

AN XY:

57763

show subpopulations

Gnomad AFR exome

AF:

0.339

Gnomad AMR exome

AF:

0.311

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.382

Gnomad SAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.446

Gnomad NFE exome

AF:

0.412

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.415

AC:

429603

AN:

1036315

Hom.:

62770

Cov.:

AF XY:

0.410

AC XY:

132183

AN XY:

322115

show subpopulations

Gnomad4 AFR exome

AF:

0.343

Gnomad4 AMR exome

AF:

0.316

Gnomad4 ASJ exome

AF:

0.414

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.412

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.420

Gnomad4 OTH exome

AF:

0.410

GnomAD4 genome

AF:

0.394

AC:

43558

AN:

110533

Hom.:

6245

Cov.:

AF XY:

0.388

AC XY:

12724

AN XY:

32819

show subpopulations

Gnomad4 AFR

AF:

0.348

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.388

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.416

Hom.:

4186

Bravo

AF:

0.386

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 25, 2012

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jan 08, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 28, 2006

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Danon disease

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Oct 20, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hypertrophic cardiomyopathy

Benign:2

Oct 10, 2022

Cohesion Phenomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Nov 24, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.0

DANN

Benign

0.45

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