rs397516737

Variant names:

• chrX-120455577-G-C
• rs397516737
• NM_002294.3:c.184-7C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002294.3(LAMP2):​c.184-7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: LAMP2 NM_002294.3 splice_region, intron
• Scores: Splicing: ADA: 0.0002611
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.264
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.184-7C>G		splice_region_variant, intron_variant	Intron 2 of 8	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.184-7C>G		splice_region_variant, intron_variant	Intron 2 of 8		NP_001116078.1
LAMP2	NM_013995.2	c.184-7C>G		splice_region_variant, intron_variant	Intron 2 of 8		NP_054701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.184-7C>G		splice_region_variant, intron_variant	Intron 2 of 8	1	NM_002294.3	ENSP00000200639.4
LAMP2	ENST00000434600.6	c.184-7C>G		splice_region_variant, intron_variant	Intron 2 of 8	1		ENSP00000408411.2
LAMP2	ENST00000371335.4	c.184-7C>G		splice_region_variant, intron_variant	Intron 2 of 8	1		ENSP00000360386.4
LAMP2	ENST00000706600.1	c.184-7C>G		splice_region_variant, intron_variant	Intron 2 of 8			ENSP00000516464.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 25, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant classified as Uncertain Significance - Favor Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.8
DANN	Benign	0.47
PhyloP100		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00026
dbscSNV1_RF	Benign	0.072
SpliceAI score (max)		0.010		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: rs397516737; hg19: chrX-119589432;