rs727503122

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002294.3(LAMP2):c.42C>T(p.Leu14Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,210,847 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 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 0.000053 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000010 ( 0 hom. 4 hem. )

Consequence

LAMP2
NM_002294.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.570

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-120469128-G-A is Benign according to our data. Variant chrX-120469128-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 163819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-120469128-G-A is described in Lovd as [Benign]. Variant chrX-120469128-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.57 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3 link	c.42C>T	p.Leu14Leu	synonymous_variant	Exon 1 of 9	ENST00000200639.9	NP_002285.1	P13473-1
LAMP2	NM_001122606.1 link	c.42C>T	p.Leu14Leu	synonymous_variant	Exon 1 of 9		NP_001116078.1	P13473-3
LAMP2	NM_013995.2 link	c.42C>T	p.Leu14Leu	synonymous_variant	Exon 1 of 9		NP_054701.1	P13473-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMP2	ENST00000200639.9 link	c.42C>T	p.Leu14Leu	synonymous_variant	Exon 1 of 9	1	NM_002294.3	ENSP00000200639.4	P13473-1
LAMP2	ENST00000434600.6 link	c.42C>T	p.Leu14Leu	synonymous_variant	Exon 1 of 9	1		ENSP00000408411.2	P13473-3
LAMP2	ENST00000371335.4 link	c.42C>T	p.Leu14Leu	synonymous_variant	Exon 1 of 9	1		ENSP00000360386.4	P13473-2
LAMP2	ENST00000706600.1 link	c.42C>T	p.Leu14Leu	synonymous_variant	Exon 1 of 9			ENSP00000516464.1	A0A9L9PXQ4

Frequencies

GnomAD3 genomes

AF:

0.0000532

AC:

AN:

112807

Hom.:

Cov.:

AF XY:

0.0000858

AC XY:

AN XY:

34955

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000937

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000274

AC:

AN:

182198

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1098040

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000132

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000713

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000532

AC:

AN:

112807

Hom.:

Cov.:

AF XY:

0.0000858

AC XY:

AN XY:

34955

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000280

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000937

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 13, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Leu14Leu in exon 1 of LAMP2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. -

not provided

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Danon disease

Benign:1

Sep 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Nov 24, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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

-0.71

CADD

Benign

4.5

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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