NM_002294.3:c.864+1647T>G

Variant names:

• chrX-120444658-A-C
• rs42890
• NM_002294.3:c.864+1647T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002294.3(LAMP2):​c.864+1647T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (16863 hom., 21176 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: LAMP2 NM_002294.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.864+1647T>G		intron_variant	Intron 6 of 8	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.864+1647T>G		intron_variant	Intron 6 of 8		NP_001116078.1
LAMP2	NM_013995.2	c.864+1647T>G		intron_variant	Intron 6 of 8		NP_054701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.864+1647T>G		intron_variant	Intron 6 of 8	1	NM_002294.3	ENSP00000200639.4

Frequencies

GnomAD3 genomes AF: 0.653 AC: 71984 AN: 110276 Hom.: 16864 Cov.: 22

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.644

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.653 AC: 72036 AN: 110330 Hom.: 16863 Cov.: 22 AF XY: 0.650 AC XY: 21176 AN XY: 32600

African (AFR) AF: 0.739 AC: 22395 AN: 30318

American (AMR) AF: 0.698 AC: 7208 AN: 10330

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 1533 AN: 2639

East Asian (EAS) AF: 0.813 AC: 2811 AN: 3459

South Asian (SAS) AF: 0.672 AC: 1743 AN: 2595

European-Finnish (FIN) AF: 0.552 AC: 3200 AN: 5792

Middle Eastern (MID) AF: 0.612 AC: 131 AN: 214

European-Non Finnish (NFE) AF: 0.599 AC: 31625 AN: 52822

Other (OTH) AF: 0.648 AC: 964 AN: 1487

Alfa AF: 0.611 Hom.: 5505

Bravo AF: 0.672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.84
PhyloP100		-1.3
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: rs42890; hg19: chrX-119578513;