rs147369153

Variant names:

• chrX-120455415-G-A
• rs147369153
• NM_002294.3:c.339C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-120455415-G-A
• chrX-120455415-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_002294.3(LAMP2):​c.339C>T​(p.Ser113Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,208,029 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 236 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 0.00066 (0 hom., 23 hem., cov: 20)
  • Exomes 𝑓: 0.00058 (0 hom. 213 hem.)
• Consequence: LAMP2 NM_002294.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:13
• Conservation: PhyloP100: 0.00500
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant X-120455415-G-A is Benign according to our data. Variant chrX-120455415-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 44426.
• BP7: Synonymous conserved (PhyloP=0.005 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 23 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.339C>T	p.Ser113Ser	synonymous	Exon 3 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.339C>T	p.Ser113Ser	synonymous	Exon 3 of 9	NP_001116078.1	P13473-3
	LAMP2	NM_013995.2		c.339C>T	p.Ser113Ser	synonymous	Exon 3 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.339C>T	p.Ser113Ser	synonymous	Exon 3 of 9	ENSP00000200639.4	P13473-1
	LAMP2	ENST00000434600.6	TSL:1	c.339C>T	p.Ser113Ser	synonymous	Exon 3 of 9	ENSP00000408411.2	P13473-3
	LAMP2	ENST00000371335.4	TSL:1	c.339C>T	p.Ser113Ser	synonymous	Exon 3 of 9	ENSP00000360386.4	P13473-2

Frequencies

GnomAD3 genomes AF: 0.000658 AC: 73 AN: 110914 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000657

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000491

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000703 AC: 129 AN: 183466 AF XY: 0.000604

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.0128

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000330

Gnomad OTH exome AF: 0.000883

GnomAD4 exome AF: 0.000583 AC: 640 AN: 1097115 Hom.: 0 Cov.: 30 AF XY: 0.000588 AC XY: 213 AN XY: 362487

African (AFR) AF: 0.00 AC: 0 AN: 26378

American (AMR) AF: 0.0000568 AC: 2 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 281 AN: 19380

East Asian (EAS) AF: 0.00 AC: 0 AN: 30198

South Asian (SAS) AF: 0.0000554 AC: 3 AN: 54128

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40532

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4134

European-Non Finnish (NFE) AF: 0.000351 AC: 295 AN: 841100

Other (OTH) AF: 0.00124 AC: 57 AN: 46059

GnomAD4 genome AF: 0.000658 AC: 73 AN: 110914 Hom.: 0 Cov.: 20 AF XY: 0.000694 AC XY: 23 AN XY: 33144

African (AFR) AF: 0.0000657 AC: 2 AN: 30458

American (AMR) AF: 0.00 AC: 0 AN: 10334

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 45 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3560

South Asian (SAS) AF: 0.00 AC: 0 AN: 2640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000491 AC: 26 AN: 52978

Other (OTH) AF: 0.00 AC: 0 AN: 1487

Alfa AF: 0.00118 Hom.: 10

Bravo AF: 0.000608

EpiCase AF: 0.000818

EpiControl AF: 0.000889

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	3	Danon disease (3)
-	-	1	Cardiomyopathy (1)
-	-	1	Cardiovascular phenotype (1)
-	1	-	Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.3
DANN	Benign	0.55
PhyloP100		0.0050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs147369153; hg19: chrX-119589270; COSMIC: COSV52353099;