rs16887018

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_007175.8(ERLIN2):c.318C>T(p.Asn106Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 1,614,062 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 138 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 132 hom. )

Consequence

ERLIN2
NM_007175.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.37

Publications

3 publications found

Variant links:

Genes affected

ERLIN2 (HGNC:1356): (ER lipid raft associated 2) This gene encodes a member of the SPFH domain-containing family of lipid raft-associated proteins. The encoded protein is localized to lipid rafts of the endoplasmic reticulum and plays a critical role in inositol 1,4,5-trisphosphate (IP3) signaling by mediating ER-associated degradation of activated IP3 receptors. Mutations in this gene are a cause of spastic paraplegia-18 (SPG18). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ERLIN2 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 18
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
juvenile primary lateral sclerosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ERLIN2 links:

ENSG00000183154 (HGNC:):

ENSG00000183154 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 8-37744590-C-T is Benign according to our data. Variant chr8-37744590-C-T is described in ClinVar as Benign. ClinVar VariationId is 129021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERLIN2	NM_007175.8 link	c.318C>T	p.Asn106Asn	synonymous_variant	Exon 6 of 12	ENST00000519638.3	NP_009106.1	O94905-1A0A384ME54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERLIN2	ENST00000519638.3 link	c.318C>T	p.Asn106Asn	synonymous_variant	Exon 6 of 12	2	NM_007175.8	ENSP00000428112.1		O94905-1

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3576

AN:

152116

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.00630

AC:

1585

AN:

251446

AF XY:

0.00473

show subpopulations

Gnomad AFR exome

AF:

0.0811

Gnomad AMR exome

AF:

0.00431

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000721

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00269

AC:

3933

AN:

1461828

Hom.:

132

Cov.:

AF XY:

0.00240

AC XY:

1742

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.0838

AC:

2805

AN:

33472

American (AMR)

AF:

0.00487

AC:

218

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000306

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000441

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00520

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000468

AC:

520

AN:

1111964

Other (OTH)

AF:

0.00518

AC:

313

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

238

476

714

952

1190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.0235

AC:

3577

AN:

152234

Hom.:

138

Cov.:

AF XY:

0.0221

AC XY:

1646

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0811

AC:

3366

AN:

41506

American (AMR)

AF:

0.00720

AC:

110

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

68032

Other (OTH)

AF:

0.0166

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

163

325

488

650

813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0131

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 06, 2016

GeneDx

Significance: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. -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Spastic paraplegia

Benign:1

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia

Benign:1

Oct 05, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

9.2

(source)

DANN

Benign

0.80

PhyloP100

3.4

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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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