rs200297370

Variant names:

• chrX-120469173-C-G
• rs200297370
• NM_002294.3:c.-4G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-120469173-C-G
• chrX-120469173-C-T
• chrX-120469173-C-A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_002294.3(LAMP2):​c.-4G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,210,408 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 77 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000089 (0 hom., 3 hem., cov: 24)
  • Exomes 𝑓: 0.00020 (0 hom. 74 hem.)
• Consequence: LAMP2 NM_002294.3 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:6
• Conservation: PhyloP100: -1.48
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant X-120469173-C-G is Benign according to our data. Variant chrX-120469173-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 44415.
• 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.-4G>C		5_prime_UTR	Exon 1 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.-4G>C		5_prime_UTR	Exon 1 of 9	NP_001116078.1	P13473-3
	LAMP2	NM_013995.2		c.-4G>C		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.-4G>C		5_prime_UTR	Exon 1 of 9	ENSP00000200639.4	P13473-1
	LAMP2	ENST00000434600.6	TSL:1	c.-4G>C		5_prime_UTR	Exon 1 of 9	ENSP00000408411.2	P13473-3
	LAMP2	ENST00000371335.4	TSL:1	c.-4G>C		5_prime_UTR	Exon 1 of 9	ENSP00000360386.4	P13473-2

Frequencies

GnomAD3 genomes AF: 0.0000889 AC: 10 AN: 112529 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000964

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000754

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000565

Gnomad OTH AF: 0.00132

GnomAD2 exomes AF: 0.000203 AC: 37 AN: 182071 AF XY: 0.000238

Gnomad AFR exome AF: 0.000154

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.00174

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000251

Gnomad NFE exome AF: 0.000161

Gnomad OTH exome AF: 0.000445

GnomAD4 exome AF: 0.000199 AC: 218 AN: 1097879 Hom.: 0 Cov.: 30 AF XY: 0.000204 AC XY: 74 AN XY: 363301

African (AFR) AF: 0.0000758 AC: 2 AN: 26400

American (AMR) AF: 0.0000852 AC: 3 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00243 AC: 47 AN: 19380

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.0000369 AC: 2 AN: 54139

European-Finnish (FIN) AF: 0.000222 AC: 9 AN: 40491

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4109

European-Non Finnish (NFE) AF: 0.000167 AC: 141 AN: 841881

Other (OTH) AF: 0.000304 AC: 14 AN: 46067

GnomAD4 genome AF: 0.0000889 AC: 10 AN: 112529 Hom.: 0 Cov.: 24 AF XY: 0.0000865 AC XY: 3 AN XY: 34683

African (AFR) AF: 0.0000964 AC: 3 AN: 31130

American (AMR) AF: 0.00 AC: 0 AN: 10679

Ashkenazi Jewish (ASJ) AF: 0.000754 AC: 2 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.00 AC: 0 AN: 2775

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53132

Other (OTH) AF: 0.00132 AC: 2 AN: 1516

Alfa AF: 0.000391 Hom.: 3

Bravo AF: 0.000132

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	2	not specified (3)
-	-	2	not provided (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Danon disease (1)
-	1	-	Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.3
DANN	Benign	0.93
PhyloP100		-1.5
PromoterAI		0.54	Over-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200297370; hg19: chrX-119603028;