rs193922648

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-120469183-AGGCGGCGAC-A
• chrX-120469183-AGGCGGCGAC-AGGCGGCGACGGCGGCGAC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002294.3(LAMP2):​c.-23_-15delGTCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,209,919 control chromosomes in the GnomAD database, including 139 homozygotes. There are 6,351 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (8 hom., 382 hem., cov: 22)
  • Exomes 𝑓: 0.017 (131 hom. 5969 hem.)
• Consequence: LAMP2 NM_002294.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.145
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant X-120469183-AGGCGGCGAC-A is Benign according to our data. Variant chrX-120469183-AGGCGGCGAC-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 36440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0132 (1492/112821) while in subpopulation NFE AF = 0.0196 (1045/53294). AF 95% confidence interval is 0.0186. There are 8 homozygotes in GnomAd4. There are 382 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 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_-15delGTCGCCGCC		5_prime_UTR	Exon 1 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.-23_-15delGTCGCCGCC		5_prime_UTR	Exon 1 of 9	NP_001116078.1	P13473-3
	LAMP2	NM_013995.2		c.-23_-15delGTCGCCGCC		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_-15delGTCGCCGCC		5_prime_UTR	Exon 1 of 9	ENSP00000200639.4	P13473-1
	LAMP2	ENST00000434600.6	TSL:1	c.-23_-15delGTCGCCGCC		5_prime_UTR	Exon 1 of 9	ENSP00000408411.2	P13473-3
	LAMP2	ENST00000371335.4	TSL:1	c.-23_-15delGTCGCCGCC		5_prime_UTR	Exon 1 of 9	ENSP00000360386.4	P13473-2

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 1493 AN: 112767 Hom.: 8 Cov.: 22

Gnomad AFR AF: 0.00360

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00112

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0126

GnomAD2 exomes AF: 0.0147 AC: 2662 AN: 181520 AF XY: 0.0143

Gnomad AFR exome AF: 0.00355

Gnomad AMR exome AF: 0.00984

Gnomad ASJ exome AF: 0.0147

Gnomad EAS exome AF: 0.000941

Gnomad FIN exome AF: 0.0195

Gnomad NFE exome AF: 0.0186

Gnomad OTH exome AF: 0.0169

GnomAD4 exome AF: 0.0167 AC: 18325 AN: 1097098 Hom.: 131 AF XY: 0.0165 AC XY: 5969 AN XY: 362610

African (AFR) AF: 0.00417 AC: 110 AN: 26385

American (AMR) AF: 0.0103 AC: 363 AN: 35187

Ashkenazi Jewish (ASJ) AF: 0.0146 AC: 283 AN: 19365

East Asian (EAS) AF: 0.00103 AC: 31 AN: 30200

South Asian (SAS) AF: 0.0172 AC: 932 AN: 54118

European-Finnish (FIN) AF: 0.0211 AC: 854 AN: 40436

Middle Eastern (MID) AF: 0.0106 AC: 43 AN: 4073

European-Non Finnish (NFE) AF: 0.0178 AC: 14965 AN: 841291

Other (OTH) AF: 0.0162 AC: 744 AN: 46043

GnomAD4 genome AF: 0.0132 AC: 1492 AN: 112821 Hom.: 8 Cov.: 22 AF XY: 0.0109 AC XY: 382 AN XY: 34997

African (AFR) AF: 0.00359 AC: 112 AN: 31189

American (AMR) AF: 0.0132 AC: 142 AN: 10718

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 33 AN: 2660

East Asian (EAS) AF: 0.00112 AC: 4 AN: 3561

South Asian (SAS) AF: 0.0101 AC: 28 AN: 2770

European-Finnish (FIN) AF: 0.0160 AC: 99 AN: 6197

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.0196 AC: 1045 AN: 53294

Other (OTH) AF: 0.0124 AC: 19 AN: 1533

Alfa AF: 0.0102 Hom.: 71

Bravo AF: 0.0127

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Danon disease (2)
-	-	1	Cardiomyopathy;C0878677:Danon disease (1)
-	-	1	not provided (1)
-	-	1	Primary familial hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
Mutation Taster		=300/0	polymorphism (auto)

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; COSMIC: COSV52351259;