rs397516587

Variant names:

• chrX-120428550-T-G
• rs397516587
• ENST00000434600.6:c.1170A>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001122606.1(LAMP2):​c.1170A>C​(p.Ile390Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,087,733 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
• Consequence: LAMP2 NM_001122606.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.77
• 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant X-120428550-T-G is Benign according to our data. Variant chrX-120428550-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 43957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.77 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	NM_002294.3	MANE Select	c.*2773A>C		3_prime_UTR	Exon 9 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.1170A>C	p.Ile390Ile	synonymous	Exon 9 of 9	NP_001116078.1	P13473-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	ENST00000434600.6	TSL:1	c.1170A>C	p.Ile390Ile	synonymous	Exon 9 of 9	ENSP00000408411.2	P13473-3
	LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.*2773A>C		3_prime_UTR	Exon 9 of 9	ENSP00000200639.4	P13473-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000602 AC: 1 AN: 166088 AF XY: 0.0000181

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1087733 Hom.: 0 Cov.: 28 AF XY: 0.00000563 AC XY: 2 AN XY: 355371

African (AFR) AF: 0.00 AC: 0 AN: 25831

American (AMR) AF: 0.00 AC: 0 AN: 33777

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19188

East Asian (EAS) AF: 0.00 AC: 0 AN: 29350

South Asian (SAS) AF: 0.00 AC: 0 AN: 51780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4118

European-Non Finnish (NFE) AF: 0.00000239 AC: 2 AN: 837670

Other (OTH) AF: 0.00 AC: 0 AN: 45663

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		2.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs397516587; hg19: chrX-119562405;