X-120427852-GAAC-G

Position:

• chrX-120427852-GAAC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002294.3(LAMP2):​c.*3468_*3470del 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

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 -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/exons	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.*3468_*3470del		3_prime_UTR_variant	9/9	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.*629_*631del		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.*3468_*3470del		3_prime_UTR_variant	9/9	1	NM_002294.3	ENSP00000200639	P3
LAMP2	ENST00000434600.6	c.*629_*631del		3_prime_UTR_variant	9/9	1		ENSP00000408411	A1

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1203 AN: 111112 Hom.: 33 Cov.: 22 AF XY: 0.0124 AC XY: 416 AN XY: 33426

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

Gnomad4 AFR AF: 0.00183

Gnomad4 AMR AF: 0.0449

Gnomad4 ASJ AF: 0.00531

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.00702

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.000888

Gnomad4 OTH AF: 0.0192

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

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

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

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: rs199705754; hg19: chrX-119561707;