rs397516750

Variant names:

• chrX-120446314-G-A
• rs397516750
• NM_002294.3:c.855C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_002294.3(LAMP2):​c.855C>T​(p.Val285Val) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: LAMP2 NM_002294.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.447
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant X-120446314-G-A is Benign according to our data. Variant chrX-120446314-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 44441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.447 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.855C>T	p.Val285Val	synonymous	Exon 6 of 9	NP_002285.1
	LAMP2	NM_001122606.1		c.855C>T	p.Val285Val	synonymous	Exon 6 of 9	NP_001116078.1
	LAMP2	NM_013995.2		c.855C>T	p.Val285Val	synonymous	Exon 6 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.855C>T	p.Val285Val	synonymous	Exon 6 of 9	ENSP00000200639.4
	LAMP2	ENST00000434600.6	TSL:1	c.855C>T	p.Val285Val	synonymous	Exon 6 of 9	ENSP00000408411.2
	LAMP2	ENST00000371335.4	TSL:1	c.855C>T	p.Val285Val	synonymous	Exon 6 of 9	ENSP00000360386.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.13e-7 AC: 1 AN: 1094923 Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 1 AN XY: 360369

African (AFR) AF: 0.00 AC: 0 AN: 26353

American (AMR) AF: 0.00 AC: 0 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19362

East Asian (EAS) AF: 0.00 AC: 0 AN: 30182

South Asian (SAS) AF: 0.00 AC: 0 AN: 54080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839129

Other (OTH) AF: 0.00 AC: 0 AN: 45996

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 28, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is not expected to have clinical significance because it does not a lter an amino acid residue and is not located near a splice junction.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.4
DANN	Benign	0.81
PhyloP100		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs397516750; hg19: chrX-119580169;