rs201209341

Variant names:

• chrX-120469179-G-A
• rs201209341
• NM_002294.3:c.-10C>T

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.-10C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000752 in 1,210,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 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 0.00027 (0 hom., 15 hem., cov: 23)
  • Exomes 𝑓: 0.000056 (0 hom. 17 hem.)
• Consequence: LAMP2 NM_002294.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 1.33
• Publications: 0 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, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant X-120469179-G-A is Benign according to our data. Variant chrX-120469179-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 138074.
• BS2: High Hemizygotes in GnomAd4 at 15 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.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_002285.1	P13473-1
	LAMP2	NM_002294.3	MANE Select	c.-10C>T		5_prime_UTR	Exon 1 of 9	NP_002285.1	P13473-1
	LAMP2	NM_001122606.1		c.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001116078.1	P13473-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000200639.4	P13473-1
	LAMP2	ENST00000434600.6	TSL:1	c.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000408411.2	P13473-3
	LAMP2	ENST00000371335.4	TSL:1	c.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000360386.4	P13473-2

Frequencies

GnomAD3 genomes AF: 0.000267 AC: 30 AN: 112485 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00244

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: 0.0000565

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000121 AC: 22 AN: 181701 AF XY: 0.000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000585

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000744

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000556 AC: 61 AN: 1097631 Hom.: 0 Cov.: 30 AF XY: 0.0000468 AC XY: 17 AN XY: 363085

African (AFR) AF: 0.00 AC: 0 AN: 26396

American (AMR) AF: 0.000426 AC: 15 AN: 35196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19373

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54131

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40465

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4091

European-Non Finnish (NFE) AF: 0.0000440 AC: 37 AN: 841718

Other (OTH) AF: 0.000195 AC: 9 AN: 46057

GnomAD4 genome AF: 0.000267 AC: 30 AN: 112485 Hom.: 0 Cov.: 23 AF XY: 0.000433 AC XY: 15 AN XY: 34631

African (AFR) AF: 0.0000321 AC: 1 AN: 31137

American (AMR) AF: 0.00244 AC: 26 AN: 10677

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.00 AC: 0 AN: 2761

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6153

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

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53098

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000332

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	2	not specified (3)
-	-	1	Cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		1.3
PromoterAI		0.019	Neutral
Mutation Taster		=300/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs201209341;

hg19: chrX-119603034;