rs377303143

Variant names:

• chrX-120439141-G-A
• rs377303143
• ENST00000371335.4:c.*13C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_013995.2(LAMP2):​c.*13C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,207,309 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000045 (0 hom. 22 hem.)
• Consequence: LAMP2 NM_013995.2 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.257
• 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant X-120439141-G-A is Benign according to our data. Variant chrX-120439141-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 179017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 22 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013995.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	NM_002294.3	MANE Select	c.1093+2589C>T		intron	N/A	NP_002285.1
	LAMP2	NM_013995.2		c.*13C>T		3_prime_UTR	Exon 9 of 9	NP_054701.1
	LAMP2	NM_001122606.1		c.1093+2589C>T		intron	N/A	NP_001116078.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	ENST00000371335.4	TSL:1	c.*13C>T		3_prime_UTR	Exon 9 of 9	ENSP00000360386.4
	LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.1093+2589C>T		intron	N/A	ENSP00000200639.4
	LAMP2	ENST00000434600.6	TSL:1	c.1093+2589C>T		intron	N/A	ENSP00000408411.2

Frequencies

GnomAD3 genomes AF: 0.0000448 AC: 5 AN: 111721 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000956

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000370

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000382 AC: 7 AN: 183341 AF XY: 0.0000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000855

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000447 AC: 49 AN: 1095537 Hom.: 0 Cov.: 29 AF XY: 0.0000609 AC XY: 22 AN XY: 361067

African (AFR) AF: 0.00 AC: 0 AN: 26349

American (AMR) AF: 0.00 AC: 0 AN: 35176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19335

East Asian (EAS) AF: 0.00 AC: 0 AN: 30084

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 54097

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40455

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4119

European-Non Finnish (NFE) AF: 0.0000548 AC: 46 AN: 839943

Other (OTH) AF: 0.0000217 AC: 1 AN: 45979

GnomAD4 genome AF: 0.0000447 AC: 5 AN: 111772 Hom.: 0 Cov.: 23 AF XY: 0.0000294 AC XY: 1 AN XY: 33986

African (AFR) AF: 0.0000325 AC: 1 AN: 30788

American (AMR) AF: 0.0000955 AC: 1 AN: 10476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3576

South Asian (SAS) AF: 0.000371 AC: 1 AN: 2693

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53164

Other (OTH) AF: 0.00 AC: 0 AN: 1525

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.2
DANN	Benign	0.84
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism

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: rs377303143; hg19: chrX-119572996;