X-120469183-AGGCGGCGAC-AGGCGGCGACGGCGGCGAC

Position:

• chrX-120469183-AGGCGGCGAC-AGGCGGCGACGGCGGCGAC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002294.3(LAMP2):​c.-15_-14insGTCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,210,108 control chromosomes in the GnomAD database, including 1 homozygotes. There are 88 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.00019 (1 hom. 85 hem.)
• Consequence: LAMP2 NM_002294.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.139

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-120469183-A-AGGCGGCGAC is Benign according to our data. Variant chrX-120469183-A-AGGCGGCGAC is described in ClinVar as [Likely_benign]. Clinvar id is 670176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP2	NM_002294.3	c.-15_-14insGTCGCCGCC		5_prime_UTR_variant	1/9	ENST00000200639.9	NP_002285.1
LAMP2	NM_001122606.1	c.-15_-14insGTCGCCGCC		5_prime_UTR_variant	1/9		NP_001116078.1
LAMP2	NM_013995.2	c.-15_-14insGTCGCCGCC		5_prime_UTR_variant	1/9		NP_054701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP2	ENST00000200639.9	c.-15_-14insGTCGCCGCC		5_prime_UTR_variant	1/9	1	NM_002294.3	ENSP00000200639	P3
LAMP2	ENST00000371335.4	c.-15_-14insGTCGCCGCC		5_prime_UTR_variant	1/9	1		ENSP00000360386	A1
LAMP2	ENST00000434600.6	c.-15_-14insGTCGCCGCC		5_prime_UTR_variant	1/9	1		ENSP00000408411	A1
LAMP2	ENST00000706600.1	c.-15_-14insGTCGCCGCC		5_prime_UTR_variant	1/9			ENSP00000516464

Frequencies

GnomAD3 genomes AF: 0.000168 AC: 19 AN: 112811 Hom.: 0 Cov.: 22 AF XY: 0.0000858 AC XY: 3 AN XY: 34967

Gnomad AFR AF: 0.000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000280

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000280

Gnomad SAS AF: 0.00144

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000563

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000248 AC: 45 AN: 181520 Hom.: 0 AF XY: 0.000359 AC XY: 24 AN XY: 66892

Gnomad AFR exome AF: 0.000385

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000289

Gnomad SAS exome AF: 0.00110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.000446

GnomAD4 exome AF: 0.000192 AC: 211 AN: 1097243 Hom.: 1 Cov.: 29 AF XY: 0.000234 AC XY: 85 AN XY: 362721

Gnomad4 AFR exome AF: 0.000341

Gnomad4 AMR exome AF: 0.000199

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000298

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.0000247

Gnomad4 NFE exome AF: 0.000122

Gnomad4 OTH exome AF: 0.000152

GnomAD4 genome AF: 0.000168 AC: 19 AN: 112865 Hom.: 0 Cov.: 22 AF XY: 0.0000856 AC XY: 3 AN XY: 35031

Gnomad4 AFR AF: 0.000256

Gnomad4 AMR AF: 0.000280

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000281

Gnomad4 SAS AF: 0.00144

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000563

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000185

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 03, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs193922648; hg19: chrX-119603038;