rs397516742

Variant names:

• chrX-120455421-A-G
• rs397516742
• NM_002294.3:c.333T>C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_002294.3(LAMP2):​c.333T>C​(p.Ile111Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,097,456 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: 0.0000036 (0 hom. 0 hem.)
• Consequence: LAMP2 NM_002294.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.654

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 -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-120455421-A-G is Benign according to our data. Variant chrX-120455421-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 44425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.654 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.333T>C	p.Ile111Ile	synonymous_variant	Exon 3 of 9	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.333T>C	p.Ile111Ile	synonymous_variant	Exon 3 of 9		NP_001116078.1
LAMP2	NM_013995.2	c.333T>C	p.Ile111Ile	synonymous_variant	Exon 3 of 9		NP_054701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.333T>C	p.Ile111Ile	synonymous_variant	Exon 3 of 9	1	NM_002294.3	ENSP00000200639.4
LAMP2	ENST00000434600.6	c.333T>C	p.Ile111Ile	synonymous_variant	Exon 3 of 9	1		ENSP00000408411.2
LAMP2	ENST00000371335.4	c.333T>C	p.Ile111Ile	synonymous_variant	Exon 3 of 9	1		ENSP00000360386.4
LAMP2	ENST00000706600.1	c.333T>C	p.Ile111Ile	synonymous_variant	Exon 3 of 9			ENSP00000516464.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1097456 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362822

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: 0.00000357

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 20

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 15, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ile111Ile in exon 3 of LAMP2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located nea r a splice junction. -

Danon disease Benign:1

Jan 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs397516742; hg19: chrX-119589276;