X-120455415-G-A

Position:

chrX-120455415-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_002294.3(LAMP2):c.339C>T(p.Ser113Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,208,029 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 236 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., 23 hem., cov: 20)

Exomes 𝑓: 0.00058 ( 0 hom. 213 hem. )

Consequence

LAMP2
NM_002294.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:11

Conservation

PhyloP100: 0.00500

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant X-120455415-G-A is Benign according to our data. Variant chrX-120455415-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 44426.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=5}. Variant chrX-120455415-G-A is described in Lovd as [Benign]. Variant chrX-120455415-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.005 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP2	NM_002294.3 linkuse as main transcript	c.339C>T	p.Ser113Ser	synonymous_variant	3/9	ENST00000200639.9	NP_002285.1	P13473-1
LAMP2	NM_001122606.1 linkuse as main transcript	c.339C>T	p.Ser113Ser	synonymous_variant	3/9		NP_001116078.1	P13473-3
LAMP2	NM_013995.2 linkuse as main transcript	c.339C>T	p.Ser113Ser	synonymous_variant	3/9		NP_054701.1	P13473-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAMP2	ENST00000200639.9 linkuse as main transcript	c.339C>T	p.Ser113Ser	synonymous_variant	3/9	1	NM_002294.3	ENSP00000200639.4	P13473-1
LAMP2	ENST00000434600.6 linkuse as main transcript	c.339C>T	p.Ser113Ser	synonymous_variant	3/9	1		ENSP00000408411.2	P13473-3
LAMP2	ENST00000371335.4 linkuse as main transcript	c.339C>T	p.Ser113Ser	synonymous_variant	3/9	1		ENSP00000360386.4	P13473-2
LAMP2	ENST00000706600.1 linkuse as main transcript	c.339C>T	p.Ser113Ser	synonymous_variant	3/9			ENSP00000516464.1	A0A9L9PXQ4

Frequencies

GnomAD3 genomes

AF:

0.000658

AC:

AN:

110914

Hom.:

Cov.:

AF XY:

0.000694

AC XY:

AN XY:

33144

show subpopulations

Gnomad AFR

AF:

0.0000657

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000491

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000703

AC:

129

AN:

183466

Hom.:

AF XY:

0.000604

AC XY:

AN XY:

67916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000330

Gnomad OTH exome

AF:

0.000883

GnomAD4 exome

AF:

0.000583

AC:

640

AN:

1097115

Hom.:

Cov.:

AF XY:

0.000588

AC XY:

213

AN XY:

362487

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000554

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000351

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.000658

AC:

AN:

110914

Hom.:

Cov.:

AF XY:

0.000694

AC XY:

AN XY:

33144

show subpopulations

Gnomad4 AFR

AF:

0.0000657

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000491

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.000608

EpiCase

AF:

0.000818

EpiControl

AF:

0.000889

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:11

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Danon disease

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Dec 22, 2015	p.Ser113Ser in exon 3 of LAMP2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.1% (53/47985) of European chromosomes, including 16 hemizygotes, by the Exome Aggregation Consor tium (ExAC, http://exac.broadinstitute.org; dbSNP rs147369153). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Hypertrophic cardiomyopathy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Aug 09, 2017

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2015

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

-0.65

CADD

Benign

8.3

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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