rs28603270

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_001122606.1	c.-421T>G		upstream_gene_variant			NP_001116078.1
LAMP2	NM_013995.2	c.-421T>G		upstream_gene_variant			NP_054701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000434600.6	c.-421T>G		upstream_gene_variant		1		ENSP00000408411.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 12852 AN: 102712 Hom.: 1631 Cov.: 19 AF XY: 0.105 AC XY: 2794 AN XY: 26566

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

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.0175

Gnomad4 EAS AF: 0.0572

Gnomad4 SAS AF: 0.0449

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.0253

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0807 Hom.: 453

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.3
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28603270; hg19: chrX-119603445;