X-120469183-AGGCGGCGAC-AGGCGGCGACGGCGGCGAC

Variant names:

• chrX-120469183-A-AGGCGGCGAC
• rs193922648
• NM_002294.3:c.-23_-15dupGTCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002294.3(LAMP2):​c.-23_-15dupGTCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,210,108 control chromosomes in the GnomAD database, including 1 homozygotes. There are 88 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.00019 (1 hom. 85 hem.)
• Consequence: LAMP2 NM_002294.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.139
• 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant X-120469183-A-AGGCGGCGAC is Benign according to our data. Variant chrX-120469183-A-AGGCGGCGAC is described in ClinVar as Likely_benign. ClinVar VariationId is 670176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002294.3. 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.-23_-15dupGTCGCCGCC		5_prime_UTR	Exon 1 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.-23_-15dupGTCGCCGCC		5_prime_UTR	Exon 1 of 9	NP_001116078.1	P13473-3
	LAMP2	NM_013995.2		c.-23_-15dupGTCGCCGCC		5_prime_UTR	Exon 1 of 9	NP_054701.1	P13473-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.-23_-15dupGTCGCCGCC		5_prime_UTR	Exon 1 of 9	ENSP00000200639.4	P13473-1
	LAMP2	ENST00000434600.6	TSL:1	c.-23_-15dupGTCGCCGCC		5_prime_UTR	Exon 1 of 9	ENSP00000408411.2	P13473-3
	LAMP2	ENST00000371335.4	TSL:1	c.-23_-15dupGTCGCCGCC		5_prime_UTR	Exon 1 of 9	ENSP00000360386.4	P13473-2

Frequencies

GnomAD3 genomes AF: 0.000168 AC: 19 AN: 112811 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000280

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000280

Gnomad SAS AF: 0.00144

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000563

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000248 AC: 45 AN: 181520 AF XY: 0.000359

Gnomad AFR exome AF: 0.000385

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000289

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.000446

GnomAD4 exome AF: 0.000192 AC: 211 AN: 1097243 Hom.: 1 Cov.: 29 AF XY: 0.000234 AC XY: 85 AN XY: 362721

African (AFR) AF: 0.000341 AC: 9 AN: 26385

American (AMR) AF: 0.000199 AC: 7 AN: 35190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19365

East Asian (EAS) AF: 0.000298 AC: 9 AN: 30201

South Asian (SAS) AF: 0.00139 AC: 75 AN: 54121

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4073

European-Non Finnish (NFE) AF: 0.000122 AC: 103 AN: 841414

Other (OTH) AF: 0.000152 AC: 7 AN: 46050

GnomAD4 genome AF: 0.000168 AC: 19 AN: 112865 Hom.: 0 Cov.: 22 AF XY: 0.0000856 AC XY: 3 AN XY: 35031

African (AFR) AF: 0.000256 AC: 8 AN: 31192

American (AMR) AF: 0.000280 AC: 3 AN: 10720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2660

East Asian (EAS) AF: 0.000281 AC: 1 AN: 3561

South Asian (SAS) AF: 0.00144 AC: 4 AN: 2772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6203

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000563 AC: 3 AN: 53323

Other (OTH) AF: 0.00 AC: 0 AN: 1533

Alfa AF: 0.00 Hom.: 71

Bravo AF: 0.000185

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs193922648; hg19: chrX-119603038;