NM_002294.3:c.156_157delACinsTT

Variant names:

• chrX-120456677-GT-AA
• rs1556114013
• NM_002294.3:c.156_157delACinsTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_002294.3(LAMP2):​c.156_157delACinsTT​(p.Arg53Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V52V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: LAMP2 NM_002294.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.43
• Publications: 0 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 -8 ACMG points.

• BP6: Variant X-120456677-GT-AA is Benign according to our data. Variant chrX-120456677-GT-AA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 532014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.156_157delACinsTT	p.Arg53Cys	missense_variant		ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.156_157delACinsTT	p.Arg53Cys	missense_variant			NP_001116078.1
LAMP2	NM_013995.2	c.156_157delACinsTT	p.Arg53Cys	missense_variant			NP_054701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.156_157delACinsTT	p.Arg53Cys	missense_variant		1	NM_002294.3	ENSP00000200639.4
LAMP2	ENST00000434600.6	c.156_157delACinsTT	p.Arg53Cys	missense_variant		1		ENSP00000408411.2
LAMP2	ENST00000371335.4	c.156_157delACinsTT	p.Arg53Cys	missense_variant		1		ENSP00000360386.4
LAMP2	ENST00000706600.1	c.156_157delACinsTT	p.Arg53Cys	missense_variant				ENSP00000516464.1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Danon disease Benign:1

Nov 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype Benign:1

Feb 27, 2025

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		2.4

Splicing

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

Other links and lift over

dbSNP: rs1556114013; hg19: chrX-119590532;