rs376215728

Variant names:

• chrX-120455550-G-A
• rs376215728
• NM_002294.3:c.204C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-120455550-G-A
• chrX-120455550-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_002294.3(LAMP2):​c.204C>T​(p.Asp68Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,092,603 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: LAMP2 NM_002294.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0940
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-120455550-G-A is Benign according to our data. Variant chrX-120455550-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1541898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.094 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002294.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	NM_002294.3	MANE Select	c.204C>T	p.Asp68Asp	synonymous	Exon 3 of 9	NP_002285.1
	LAMP2	NM_001122606.1		c.204C>T	p.Asp68Asp	synonymous	Exon 3 of 9	NP_001116078.1
	LAMP2	NM_013995.2		c.204C>T	p.Asp68Asp	synonymous	Exon 3 of 9	NP_054701.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.204C>T	p.Asp68Asp	synonymous	Exon 3 of 9	ENSP00000200639.4
	LAMP2	ENST00000434600.6	TSL:1	c.204C>T	p.Asp68Asp	synonymous	Exon 3 of 9	ENSP00000408411.2
	LAMP2	ENST00000371335.4	TSL:1	c.204C>T	p.Asp68Asp	synonymous	Exon 3 of 9	ENSP00000360386.4

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1092603 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 358067

African (AFR) AF: 0.00 AC: 0 AN: 26295

American (AMR) AF: 0.00 AC: 0 AN: 35199

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.00 AC: 0 AN: 30187

South Asian (SAS) AF: 0.00 AC: 0 AN: 53990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4121

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837000

Other (OTH) AF: 0.0000218 AC: 1 AN: 45927

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Danon disease Benign:1

Oct 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.8
DANN	Benign	0.28
PhyloP100		-0.094
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs376215728; hg19: chrX-119589405;