chrX-120426285-T-C

Variant names:

• chrX-120426285-T-C
• rs2748
• NM_002294.3:c.*5038A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002294.3(LAMP2):​c.*5038A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.29 (4018 hom., 7042 hem., cov: 18)
• Consequence: LAMP2 NM_002294.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.00
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• Danon disease

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-120426285-T-C is Benign according to our data. Variant chrX-120426285-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 367737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.*5038A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.*2199A>G		3_prime_UTR_variant	Exon 9 of 9		NP_001116078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.*5038A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_002294.3	ENSP00000200639.4

Frequencies

GnomAD3 genomes AF: 0.293 AC: 29906 AN: 102238 Hom.: 4023 Cov.: 18

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.291

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 29899 AN: 102290 Hom.: 4018 Cov.: 18 AF XY: 0.277 AC XY: 7042 AN XY: 25416

African (AFR) AF: 0.103 AC: 2897 AN: 28116

American (AMR) AF: 0.248 AC: 2266 AN: 9127

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 896 AN: 2494

East Asian (EAS) AF: 0.382 AC: 1243 AN: 3253

South Asian (SAS) AF: 0.358 AC: 754 AN: 2104

European-Finnish (FIN) AF: 0.368 AC: 1798 AN: 4886

Middle Eastern (MID) AF: 0.395 AC: 85 AN: 215

European-Non Finnish (NFE) AF: 0.385 AC: 19295 AN: 50115

Other (OTH) AF: 0.293 AC: 396 AN: 1353

Alfa AF: 0.350 Hom.: 41858

Bravo AF: 0.280

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Danon disease Benign:1

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. -

Hypertrophic cardiomyopathy Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.65
PhyloP100		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2748; hg19: chrX-119560140;