X-120426744-T-C

Variant names:

• chrX-120426744-T-C
• rs42885
• NM_002294.3:c.*4579A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_002294.3(LAMP2):​c.*4579A>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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (16428 hom., 20919 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: LAMP2 NM_002294.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.0950
• Publications: 4 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-120426744-T-C is Benign according to our data. Variant chrX-120426744-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 367743.Status of the report is criteria_provided_single_submitter, 1 stars.

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.*4579A>G		3_prime_UTR	Exon 9 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.*1740A>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.*4579A>G		3_prime_UTR	Exon 9 of 9	ENSP00000200639.4	P13473-1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 70932 AN: 110702 Hom.: 16429 Cov.: 23

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.631

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.641 AC: 70985 AN: 110755 Hom.: 16428 Cov.: 23 AF XY: 0.634 AC XY: 20919 AN XY: 32995

African (AFR) AF: 0.755 AC: 22997 AN: 30469

American (AMR) AF: 0.684 AC: 7118 AN: 10403

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1432 AN: 2631

East Asian (EAS) AF: 0.815 AC: 2874 AN: 3527

South Asian (SAS) AF: 0.670 AC: 1790 AN: 2672

European-Finnish (FIN) AF: 0.478 AC: 2809 AN: 5882

Middle Eastern (MID) AF: 0.568 AC: 121 AN: 213

European-Non Finnish (NFE) AF: 0.577 AC: 30456 AN: 52777

Other (OTH) AF: 0.635 AC: 959 AN: 1510

Alfa AF: 0.592 Hom.: 4307

Bravo AF: 0.665

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	-0.97
CADD	Benign	2.0
DANN	Benign	0.60
PhyloP100		0.095

Splicing

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

Other links and lift over

dbSNP: rs42885; hg19: chrX-119560599;