chrX-120469590-A-C

Variant names:

• chrX-120469590-A-C
• rs28603270
• ENST00000434600.6:c.-421T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001122606.1(LAMP2):​c.-421T>G variant causes a upstream gene 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 Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1636 hom., 2808 hem., cov: 19)
• Consequence: LAMP2 NM_001122606.1 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347
• Publications: 3 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant X-120469590-A-C is Benign according to our data. Variant chrX-120469590-A-C is described in ClinVar as Benign. ClinVar VariationId is 683597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122606.1. 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_001122606.1		c.-421T>G		upstream_gene	N/A	NP_001116078.1
	LAMP2	NM_013995.2		c.-421T>G		upstream_gene	N/A	NP_054701.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	ENST00000434600.6	TSL:1	c.-421T>G		upstream_gene	N/A	ENSP00000408411.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 12852 AN: 102712 Hom.: 1631 Cov.: 19

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0175

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.0913

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.125 AC: 12879 AN: 102735 Hom.: 1636 Cov.: 19 AF XY: 0.106 AC XY: 2808 AN XY: 26595

African (AFR) AF: 0.376 AC: 10353 AN: 27520

American (AMR) AF: 0.0687 AC: 631 AN: 9191

Ashkenazi Jewish (ASJ) AF: 0.0175 AC: 45 AN: 2565

East Asian (EAS) AF: 0.0572 AC: 187 AN: 3267

South Asian (SAS) AF: 0.0449 AC: 101 AN: 2248

European-Finnish (FIN) AF: 0.0161 AC: 75 AN: 4657

Middle Eastern (MID) AF: 0.0933 AC: 18 AN: 193

European-Non Finnish (NFE) AF: 0.0253 AC: 1294 AN: 51051

Other (OTH) AF: 0.117 AC: 161 AN: 1374

Alfa AF: 0.0807 Hom.: 453

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.3
DANN	Benign	0.94
PhyloP100		0.35
PromoterAI		0.059	Neutral

Splicing

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

Other links and lift over

dbSNP: rs28603270; hg19: chrX-119603445;