rs727503121

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002294.3(LAMP2):c.65-13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000611 in 949,102 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 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 0.000036 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000064 ( 0 hom. 11 hem. )

Consequence

LAMP2
NM_002294.3 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -1.13

Publications

1 publications found

Variant links:

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

LAMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-120456782-A-T is Benign according to our data. Variant chrX-120456782-A-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 163818.

BS2

High Hemizygotes in GnomAdExome4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
LAMP2	NM_002294.3 link	c.65-13T>A	intron_variant	Intron 1 of 8	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1 link	c.65-13T>A	intron_variant	Intron 1 of 8		NP_001116078.1
LAMP2	NM_013995.2 link	c.65-13T>A	intron_variant	Intron 1 of 8		NP_054701.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
LAMP2	ENST00000200639.9 link	c.65-13T>A	intron_variant	Intron 1 of 8	1	NM_002294.3	ENSP00000200639.4
LAMP2	ENST00000434600.6 link	c.65-13T>A	intron_variant	Intron 1 of 8	1		ENSP00000408411.2
LAMP2	ENST00000371335.4 link	c.65-13T>A	intron_variant	Intron 1 of 8	1		ENSP00000360386.4
LAMP2	ENST00000706600.1 link	c.65-13T>A	intron_variant	Intron 1 of 8			ENSP00000516464.1

Frequencies

GnomAD3 genomes

AF:

0.0000358

AC:

AN:

111709

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000221

AC:

AN:

135641

AF XY:

0.00

show subpopulations

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:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000645

AC:

AN:

837393

Hom.:

Cov.:

AF XY:

0.0000520

AC XY:

AN XY:

211409

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20737

American (AMR)

AF:

0.0000318

AC:

AN:

31487

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17193

East Asian (EAS)

AF:

0.00

AC:

AN:

26900

South Asian (SAS)

AF:

0.00

AC:

AN:

41884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37607

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2575

European-Non Finnish (NFE)

AF:

0.0000852

AC:

AN:

622113

Other (OTH)

AF:

0.00

AC:

AN:

36897

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000358

AC:

AN:

111709

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33903

show subpopulations

African (AFR)

AF:

0.0000326

AC:

AN:

30701

American (AMR)

AF:

0.00

AC:

AN:

10433

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3604

South Asian (SAS)

AF:

0.00

AC:

AN:

2723

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5985

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53189

Other (OTH)

AF:

0.00

AC:

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Oct 30, 2017

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Nov 03, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.65-13T>A variant in LAMP2 has not been previously reported in individuals with cardiomyopathy. Data from large population studies are insufficient to asse ss the frequency of this variant. This variant is located in the 3' splice regio n. Computational tools do not suggest an impact to splicing. However, this infor mation is not predictive enough to determine pathogenicity. In summary, the clin ical significance of the c.65-13T>A variant is uncertain.

Danon disease

Benign:1

Oct 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.056

(source)

DANN

Benign

0.49

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over