X-120426744-T-C

Position:

• chrX-120426744-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_002294.3(LAMP2):​c.*4579A>G variant causes a 3 prime UTR 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (16428 hom., 20919 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: LAMP2 NM_002294.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.0950

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-120426744-T-C is Benign according to our data. Variant chrX-120426744-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 367743.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.*4579A>G		3_prime_UTR_variant	9/9	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.*1740A>G		3_prime_UTR_variant	9/9		NP_001116078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.*4579A>G		3_prime_UTR_variant	9/9	1	NM_002294.3	ENSP00000200639	P3

Frequencies

GnomAD3 genomes AF: 0.641 AC: 70932 AN: 110702 Hom.: 16429 Cov.: 23 AF XY: 0.633 AC XY: 20859 AN XY: 32932

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.631

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.641 AC: 70985 AN: 110755 Hom.: 16428 Cov.: 23 AF XY: 0.634 AC XY: 20919 AN XY: 32995

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.635

Alfa AF: 0.592 Hom.: 4307

Bravo AF: 0.665

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Danon disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hypertrophic cardiomyopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs42885; hg19: chrX-119560599;