X-120427852-GAAC-G

Variant names:

• chrX-120427852-GAAC-G
• rs199705754
• NM_002294.3:c.*3468_*3470delGTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002294.3(LAMP2):​c.*3468_*3470delGTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 111,164 control chromosomes in the GnomAD database, including 33 homozygotes. There are 415 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (33 hom., 415 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: LAMP2 NM_002294.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.17
• 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant X-120427852-GAAC-G is Benign according to our data. Variant chrX-120427852-GAAC-G is described in ClinVar as [Likely_benign]. Clinvar id is 367748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.*3468_*3470delGTT		3_prime_UTR_variant	Exon 9 of 9	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.*629_*631delGTT		3_prime_UTR_variant	Exon 9 of 9		NP_001116078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.*3468_*3470delGTT		3_prime_UTR_variant	Exon 9 of 9	1	NM_002294.3	ENSP00000200639.4
LAMP2	ENST00000434600.6	c.*629_*631delGTT		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000408411.2

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1203 AN: 111112 Hom.: 33 Cov.: 22

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.00531

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.00663

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000888

Gnomad OTH AF: 0.0194

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

GnomAD4 genome AF: 0.0108 AC: 1203 AN: 111164 Hom.: 33 Cov.: 22 AF XY: 0.0124 AC XY: 415 AN XY: 33488

African (AFR) AF: 0.00183 AC: 56 AN: 30660

American (AMR) AF: 0.0449 AC: 470 AN: 10458

Ashkenazi Jewish (ASJ) AF: 0.00531 AC: 14 AN: 2638

East Asian (EAS) AF: 0.115 AC: 405 AN: 3534

South Asian (SAS) AF: 0.00702 AC: 19 AN: 2706

European-Finnish (FIN) AF: 0.0279 AC: 163 AN: 5851

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000888 AC: 47 AN: 52908

Other (OTH) AF: 0.0192 AC: 29 AN: 1513

Alfa AF: 0.00130 Hom.: 8

Bravo AF: 0.0134

Asia WGS AF: 0.0490 AC: 122 AN: 2519

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Danon disease Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 20, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs199705754; hg19: chrX-119561707;