NM_002294.3:c.443A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4BP6BS2

The NM_002294.3(LAMP2):c.443A>G(p.Asn148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,202,195 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 3 hem. )

Consequence

LAMP2
NM_002294.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 2.19

Publications

0 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp

LAMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.31337184).

BP6

Variant X-120449083-T-C is Benign according to our data. Variant chrX-120449083-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 578311.

BS2

High Hemizygotes in GnomAdExome4 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMP2	NM_002294.3	MANE Select	c.443A>G	p.Asn148Ser	missense	Exon 4 of 9	NP_002285.1	P13473-1
LAMP2	NM_001122606.1		c.443A>G	p.Asn148Ser	missense	Exon 4 of 9	NP_001116078.1	P13473-3
LAMP2	NM_013995.2		c.443A>G	p.Asn148Ser	missense	Exon 4 of 9	NP_054701.1	P13473-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.443A>G	p.Asn148Ser	missense	Exon 4 of 9	ENSP00000200639.4	P13473-1
LAMP2	ENST00000434600.6	TSL:1	c.443A>G	p.Asn148Ser	missense	Exon 4 of 9	ENSP00000408411.2	P13473-3
LAMP2	ENST00000371335.4	TSL:1	c.443A>G	p.Asn148Ser	missense	Exon 4 of 9	ENSP00000360386.4	P13473-2

Frequencies

GnomAD3 genomes

AF:

0.0000533

AC:

AN:

112554

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000112

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

182411

AF XY:

0.0000149

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:

0.0000368

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000734

AC:

AN:

1089641

Hom.:

Cov.:

AF XY:

0.00000845

AC XY:

AN XY:

355229

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26249

American (AMR)

AF:

0.00

AC:

AN:

35132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19326

East Asian (EAS)

AF:

0.00

AC:

AN:

30152

South Asian (SAS)

AF:

0.00

AC:

AN:

53740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4062

European-Non Finnish (NFE)

AF:

0.00000959

AC:

AN:

834633

Other (OTH)

AF:

0.00

AC:

AN:

45827

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.0000533

AC:

AN:

112554

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30988

American (AMR)

AF:

0.00

AC:

AN:

10582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.00

AC:

AN:

3634

South Asian (SAS)

AF:

0.00

AC:

AN:

2767

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000112

AC:

AN:

53348

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000453

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Danon disease (2)

Cardiovascular phenotype (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

CardioboostCm

Benign

0.053

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.79

M_CAP

Benign

0.033

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.0

PhyloP100

2.2

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.083

Sift

Uncertain

0.010

Sift4G

Uncertain

0.023

Polyphen

0.93

Vest4

0.32

MutPred

0.66

Loss of stability (P = 0.0641)

MVP

0.60

MPC

0.50

ClinPred

0.65

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.41

Mutation Taster

=99/1

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over