chrX-120426362-T-C

Variant names:

• chrX-120426362-T-C
• rs765371462
• NM_002294.3:c.*4961A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_002294.3(LAMP2):​c.*4961A>G 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 Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: 𝑓 0.00040 (0 hom., 10 hem., cov: 20)
• Consequence: LAMP2 NM_002294.3 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:1
• Conservation: PhyloP100: 0.911
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant X-120426362-T-C is Benign according to our data. Variant chrX-120426362-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 367739.
• BS2: High Hemizygotes in GnomAd4 at 10 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.*4961A>G		3_prime_UTR	Exon 9 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.*2122A>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.*4961A>G		3_prime_UTR	Exon 9 of 9	ENSP00000200639.4	P13473-1

Frequencies

GnomAD3 genomes AF: 0.000405 AC: 44 AN: 108597 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000201

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: 0.000764

Gnomad OTH AF: 0.000695

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

GnomAD4 genome AF: 0.000405 AC: 44 AN: 108650 Hom.: 0 Cov.: 20 AF XY: 0.000323 AC XY: 10 AN XY: 30930

African (AFR) AF: 0.0000335 AC: 1 AN: 29845

American (AMR) AF: 0.000201 AC: 2 AN: 9962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2600

East Asian (EAS) AF: 0.00 AC: 0 AN: 3494

South Asian (SAS) AF: 0.00 AC: 0 AN: 2460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5590

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

European-Non Finnish (NFE) AF: 0.000764 AC: 40 AN: 52346

Other (OTH) AF: 0.000686 AC: 1 AN: 1458

Alfa AF: 0.000641 Hom.: 2

Bravo AF: 0.000461

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	2	-	Danon disease (2)
-	1	-	Hypertrophic cardiomyopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.6
DANN	Benign	0.74
PhyloP100		0.91

Splicing

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

Other links and lift over

dbSNP: rs765371462; hg19: chrX-119560217;