rs3827478

Positions:

chrX-120428577-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000200639.9(LAMP2):c.*2746A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,197,967 control chromosomes in the GnomAD database, including 126 homozygotes. There are 2,297 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 0.014 ( 19 hom., 490 hem., cov: 23)

Exomes 𝑓: 0.0049 ( 107 hom. 1807 hem. )

Consequence

LAMP2
ENST00000200639.9 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.524

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-120428577-T-C is Benign according to our data. Variant chrX-120428577-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 43956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-120428577-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP2	NM_002294.3 linkuse as main transcript	c.*2746A>G		3_prime_UTR_variant	9/9	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1 linkuse as main transcript	c.1143A>G	p.Ala381=	synonymous_variant	9/9		NP_001116078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000434600.6 linkuse as main transcript	c.1143A>G	p.Ala381=	synonymous_variant	9/9	1		ENSP00000408411	A1	P13473-3
LAMP2	ENST00000200639.9 linkuse as main transcript	c.*2746A>G		3_prime_UTR_variant	9/9	1	NM_002294.3	ENSP00000200639	P3	P13473-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

1595

AN:

111836

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

490

AN XY:

34070

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00420

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.0244

Gnomad FIN

AF:

0.00131

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000377

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0102

AC:

1644

AN:

161044

Hom.:

AF XY:

0.00812

AC XY:

413

AN XY:

50868

show subpopulations

Gnomad AFR exome

AF:

0.0373

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0702

Gnomad SAS exome

AF:

0.0186

Gnomad FIN exome

AF:

0.00161

Gnomad NFE exome

AF:

0.000766

Gnomad OTH exome

AF:

0.00541

GnomAD4 exome

AF:

0.00488

AC:

5301

AN:

1086077

Hom.:

107

Cov.:

AF XY:

0.00511

AC XY:

1807

AN XY:

353869

show subpopulations

Gnomad4 AFR exome

AF:

0.0403

Gnomad4 AMR exome

AF:

0.00272

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0845

Gnomad4 SAS exome

AF:

0.0190

Gnomad4 FIN exome

AF:

0.00169

Gnomad4 NFE exome

AF:

0.000245

Gnomad4 OTH exome

AF:

0.00920

GnomAD4 genome

AF:

0.0143

AC:

1598

AN:

111890

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

490

AN XY:

34134

show subpopulations

Gnomad4 AFR

AF:

0.0382

Gnomad4 AMR

AF:

0.00429

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0725

Gnomad4 SAS

AF:

0.0252

Gnomad4 FIN

AF:

0.00131

Gnomad4 NFE

AF:

0.000377

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00720

Hom.:

Bravo

AF:

0.0163

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 30, 2011	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Danon disease

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Hypertrophic cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.81

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