rs376215728

Positions:

• chrX-120455550-G-A
• chrX-120455550-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_002294.3(LAMP2):​c.204C>T​(p.Asp68Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,092,603 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: 20)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: LAMP2 NM_002294.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0940

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-120455550-G-A is Benign according to our data. Variant chrX-120455550-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1541898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.094 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.204C>T	p.Asp68Asp	synonymous_variant	3/9	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.204C>T	p.Asp68Asp	synonymous_variant	3/9		NP_001116078.1
LAMP2	NM_013995.2	c.204C>T	p.Asp68Asp	synonymous_variant	3/9		NP_054701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.204C>T	p.Asp68Asp	synonymous_variant	3/9	1	NM_002294.3	ENSP00000200639.4
LAMP2	ENST00000434600.6	c.204C>T	p.Asp68Asp	synonymous_variant	3/9	1		ENSP00000408411.2
LAMP2	ENST00000371335.4	c.204C>T	p.Asp68Asp	synonymous_variant	3/9	1		ENSP00000360386.4
LAMP2	ENST00000706600.1	c.204C>T	p.Asp68Asp	synonymous_variant	3/9			ENSP00000516464.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1092603 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 358067

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000218

GnomAD4 genome Cov.: 20

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Danon disease Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.8
DANN	Benign	0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs376215728; hg19: chrX-119589405;