Variant rs141560438 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_020919.4(ALS2):c.2841+48del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,609,216 control chromosomes in the GnomAD database, including 1,885 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 112 hom., cov: 31)

Exomes 𝑓: 0.047 ( 1773 hom. )

Consequence

ALS2
NM_020919.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.954

Variant links:

Genes affected

ALS2 (HGNC:443): (alsin Rho guanine nucleotide exchange factor ALS2) The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ALS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-201728463-TA-T is Benign according to our data. Variant chr2-201728463-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 261371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALS2	NM_020919.4 linkuse as main transcript	c.2841+48del		intron_variant		ENST00000264276.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALS2	ENST00000264276.11 linkuse as main transcript	c.2841+48del		intron_variant		1	NM_020919.4	P4	Q96Q42-1

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

5235

AN:

152148

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.0335

Gnomad EAS

AF:

0.0125

Gnomad SAS

AF:

0.0404

Gnomad FIN

AF:

0.0314

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0501

Gnomad OTH

AF:

0.0387

GnomAD3 exomes

AF:

0.0392

AC:

9758

AN:

249202

Hom.:

256

AF XY:

0.0415

AC XY:

5606

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0260

Gnomad ASJ exome

AF:

0.0359

Gnomad EAS exome

AF:

0.0115

Gnomad SAS exome

AF:

0.0471

Gnomad FIN exome

AF:

0.0328

Gnomad NFE exome

AF:

0.0505

Gnomad OTH exome

AF:

0.0460

GnomAD4 exome

AF:

0.0469

AC:

68278

AN:

1456950

Hom.:

1773

Cov.:

AF XY:

0.0473

AC XY:

34336

AN XY:

725236

show subpopulations

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.0276

Gnomad4 ASJ exome

AF:

0.0363

Gnomad4 EAS exome

AF:

0.00800

Gnomad4 SAS exome

AF:

0.0491

Gnomad4 FIN exome

AF:

0.0342

Gnomad4 NFE exome

AF:

0.0509

Gnomad4 OTH exome

AF:

0.0454

GnomAD4 genome

AF:

0.0344

AC:

5236

AN:

152266

Hom.:

112

Cov.:

AF XY:

0.0330

AC XY:

2456

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.0315

Gnomad4 ASJ

AF:

0.0335

Gnomad4 EAS

AF:

0.0125

Gnomad4 SAS

AF:

0.0409

Gnomad4 FIN

AF:

0.0314

Gnomad4 NFE

AF:

0.0501

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.0260

Hom.:

Bravo

AF:

0.0328

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over