Variant rs3219170 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020919.4(ALS2):c.4581-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 1,485,640 control chromosomes in the GnomAD database, including 631,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 61068 hom., cov: 32)

Exomes 𝑓: 0.92 ( 570881 hom. )

Consequence

ALS2
NM_020919.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.198

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:

ALS2 (HGNC:):

ALS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-201705509-A-G is Benign according to our data. Variant chr2-201705509-A-G is described in ClinVar as [Benign]. Clinvar id is 261379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALS2	NM_020919.4 linkuse as main transcript	c.4581-48T>C		intron_variant		ENST00000264276.11	NP_065970.2	Q96Q42-1A8K4R4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALS2	ENST00000264276.11 linkuse as main transcript	c.4581-48T>C		intron_variant		1	NM_020919.4	ENSP00000264276.6		Q96Q42-1

Frequencies

GnomAD3 genomes

AF:

0.894

AC:

136002

AN:

152088

Hom.:

61021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.819

Gnomad AMI

AF:

0.981

Gnomad AMR

AF:

0.882

Gnomad ASJ

AF:

0.914

Gnomad EAS

AF:

0.984

Gnomad SAS

AF:

0.959

Gnomad FIN

AF:

0.961

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.919

Gnomad OTH

AF:

0.880

GnomAD3 exomes

AF:

0.923

AC:

221992

AN:

240488

Hom.:

102622

AF XY:

0.928

AC XY:

121188

AN XY:

130660

show subpopulations

Gnomad AFR exome

AF:

0.821

Gnomad AMR exome

AF:

0.893

Gnomad ASJ exome

AF:

0.916

Gnomad EAS exome

AF:

0.986

Gnomad SAS exome

AF:

0.960

Gnomad FIN exome

AF:

0.954

Gnomad NFE exome

AF:

0.921

Gnomad OTH exome

AF:

0.920

GnomAD4 exome

AF:

0.925

AC:

1233347

AN:

1333434

Hom.:

570881

Cov.:

AF XY:

0.927

AC XY:

621142

AN XY:

670362

show subpopulations

Gnomad4 AFR exome

AF:

0.825

Gnomad4 AMR exome

AF:

0.890

Gnomad4 ASJ exome

AF:

0.914

Gnomad4 EAS exome

AF:

0.991

Gnomad4 SAS exome

AF:

0.959

Gnomad4 FIN exome

AF:

0.954

Gnomad4 NFE exome

AF:

0.923

Gnomad4 OTH exome

AF:

0.922

GnomAD4 genome

AF:

0.894

AC:

136108

AN:

152206

Hom.:

61068

Cov.:

AF XY:

0.898

AC XY:

66792

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.819

Gnomad4 AMR

AF:

0.882

Gnomad4 ASJ

AF:

0.914

Gnomad4 EAS

AF:

0.985

Gnomad4 SAS

AF:

0.959

Gnomad4 FIN

AF:

0.961

Gnomad4 NFE

AF:

0.919

Gnomad4 OTH

AF:

0.880

Alfa

AF:

0.904

Hom.:

12044

Bravo

AF:

0.885

Asia WGS

AF:

0.958

AC:

3327

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Infantile-onset ascending hereditary spastic paralysis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Juvenile primary lateral sclerosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Amyotrophic lateral sclerosis type 2, juvenile

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.1

DANN

Benign

0.78

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

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