NM_002294.3:c.*5048A>T

Variant names:

• chrX-120426275-T-A
• rs113285013
• NM_002294.3:c.*5048A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002294.3(LAMP2):​c.*5048A>T 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 0.0074 (7 hom., 156 hem., cov: 18)
• Consequence: LAMP2 NM_002294.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.325
• 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-120426275-T-A is Benign according to our data. Variant chrX-120426275-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 367736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00739 (759/102697) while in subpopulation AFR AF = 0.0249 (697/28042). AF 95% confidence interval is 0.0233. There are 7 homozygotes in GnomAd4. There are 156 alleles in the male GnomAd4 subpopulation. Median coverage is 18. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	NM_002294.3	MANE Select	c.*5048A>T		3_prime_UTR	Exon 9 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.*2209A>T		3_prime_UTR	Exon 9 of 9	NP_001116078.1	P13473-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.*5048A>T		3_prime_UTR	Exon 9 of 9	ENSP00000200639.4	P13473-1

Frequencies

GnomAD3 genomes AF: 0.00739 AC: 759 AN: 102644 Hom.: 7 Cov.: 18

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00476

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000158

Gnomad OTH AF: 0.00828

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

GnomAD4 genome AF: 0.00739 AC: 759 AN: 102697 Hom.: 7 Cov.: 18 AF XY: 0.00609 AC XY: 156 AN XY: 25633

African (AFR) AF: 0.0249 AC: 697 AN: 28042

American (AMR) AF: 0.00475 AC: 43 AN: 9047

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2503

East Asian (EAS) AF: 0.00 AC: 0 AN: 3322

South Asian (SAS) AF: 0.00 AC: 0 AN: 2101

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000158 AC: 8 AN: 50482

Other (OTH) AF: 0.00817 AC: 11 AN: 1347

Alfa AF: 0.00527 Hom.: 14

Bravo AF: 0.00880

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Danon disease (1)
-	-	1	Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.67
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs113285013; hg19: chrX-119560130;