X-120434622-G-C

Variant names:

• chrX-120434622-G-C
• rs5909722
• NM_002294.3:c.1094-3160C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002294.3(LAMP2):​c.1094-3160C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 110,811 control chromosomes in the GnomAD database, including 3,975 homozygotes. There are 9,301 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (3975 hom., 9301 hem., cov: 23)
• Consequence: LAMP2 NM_002294.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.1094-3160C>G		intron_variant	Intron 8 of 8	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.1094-5996C>G		intron_variant	Intron 8 of 8		NP_001116078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.1094-3160C>G		intron_variant	Intron 8 of 8	1	NM_002294.3	ENSP00000200639.4
LAMP2	ENST00000434600.6	c.1094-5996C>G		intron_variant	Intron 8 of 8	1		ENSP00000408411.2
LAMP2	ENST00000706600.1	c.1094-1936C>G		intron_variant	Intron 8 of 8			ENSP00000516464.1
LAMP2	ENST00000486593.5	n.*79-3160C>G		intron_variant	Intron 6 of 6	5		ENSP00000431526.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 31984 AN: 110752 Hom.: 3980 Cov.: 23

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.403

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.289 AC: 31975 AN: 110811 Hom.: 3975 Cov.: 23 AF XY: 0.281 AC XY: 9301 AN XY: 33065

African (AFR) AF: 0.0896 AC: 2751 AN: 30720

American (AMR) AF: 0.247 AC: 2564 AN: 10395

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 946 AN: 2616

East Asian (EAS) AF: 0.386 AC: 1345 AN: 3488

South Asian (SAS) AF: 0.366 AC: 972 AN: 2653

European-Finnish (FIN) AF: 0.370 AC: 2106 AN: 5699

Middle Eastern (MID) AF: 0.400 AC: 86 AN: 215

European-Non Finnish (NFE) AF: 0.387 AC: 20461 AN: 52834

Other (OTH) AF: 0.300 AC: 456 AN: 1521

Alfa AF: 0.338 Hom.: 2284

Bravo AF: 0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.53
PhyloP100		1.0
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: rs5909722; hg19: chrX-119568477;