rs3827478

chrX-120428577-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000434600.6(LAMP2):c.1143A>G(p.Ala381=) variant causes a synonymous 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 ENST00000434600.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.524

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]

ACMG classification

Verdict is Benign. Variant got -21 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].
• BP7: Synonymous conserved (PhyloP=0.524 with no splicing effect.
• 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	UniProt
LAMP2	NM_002294.3	c.*2746A>G		3_prime_UTR_variant	9/9	ENST00000200639.9
LAMP2	NM_001122606.1	c.1143A>G	p.Ala381=	synonymous_variant	9/9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 1595 AN: 111836 Hom.: 19 Cov.: 23 AF XY: 0.0144 AC XY: 490 AN XY: 34070

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.: 36 AF XY: 0.00812 AC XY: 413 AN XY: 50868

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.: 28 AF XY: 0.00511 AC XY: 1807 AN XY: 353869

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.: 19 Cov.: 23 AF XY: 0.0144 AC XY: 490 AN XY: 34134

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.: 43

Bravo AF: 0.0163

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic 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	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Danon disease Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

not provided Benign:1

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	17
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

Other links and lift over

dbSNP: rs3827478; hg19: chrX-119562432; COSMIC: COSV52355510; COSMIC: COSV52355510;