rs142200759

Variant names:

• chrX-120426761-T-C
• rs142200759
• NM_002294.3:c.*4562A>G

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.*4562A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 112,107 control chromosomes in the GnomAD database, including 33 homozygotes. There are 442 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.014 (33 hom., 442 hem., cov: 22)
• Consequence: LAMP2 NM_002294.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.934
• 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: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-120426761-T-C is Benign according to our data. Variant chrX-120426761-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 367744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (1576/112107) while in subpopulation AFR AF = 0.0486 (1502/30914). AF 95% confidence interval is 0.0465. There are 33 homozygotes in GnomAd4. There are 442 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 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.*4562A>G		3_prime_UTR	Exon 9 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.*1723A>G		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.*4562A>G		3_prime_UTR	Exon 9 of 9	ENSP00000200639.4	P13473-1

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 1573 AN: 112056 Hom.: 33 Cov.: 22

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000226

Gnomad OTH AF: 0.0140

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

GnomAD4 genome AF: 0.0141 AC: 1576 AN: 112107 Hom.: 33 Cov.: 22 AF XY: 0.0129 AC XY: 442 AN XY: 34283

African (AFR) AF: 0.0486 AC: 1502 AN: 30914

American (AMR) AF: 0.00379 AC: 40 AN: 10547

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.00 AC: 0 AN: 2724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6115

Middle Eastern (MID) AF: 0.00461 AC: 1 AN: 217

European-Non Finnish (NFE) AF: 0.000226 AC: 12 AN: 53144

Other (OTH) AF: 0.0138 AC: 21 AN: 1524

Alfa AF: 0.0105 Hom.: 35

Bravo AF: 0.0160

ClinVar

ClinVar submissions as Germline

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	-0.84
CADD	Benign	6.4
DANN	Benign	0.50
PhyloP100		0.93

Splicing

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

Other links and lift over

dbSNP: rs142200759; hg19: chrX-119560616;