Variant rs761546961 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000032.5(ALAS2):c.1563C>T(p.Ser521Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,097,899 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000021 ( 0 hom. 5 hem. )

Consequence

ALAS2
NM_000032.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.191

Variant links:

Genes affected

ALAS2 (HGNC:397): (5'-aminolevulinate synthase 2) The product of this gene specifies an erythroid-specific mitochondrially located enzyme. The encoded protein catalyzes the first step in the heme biosynthetic pathway. Defects in this gene cause X-linked pyridoxine-responsive sideroblastic anemia. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ALAS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant X-55013523-G-A is Benign according to our data. Variant chrX-55013523-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 254728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.191 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALAS2	NM_000032.5 linkuse as main transcript	c.1563C>T	p.Ser521Ser	synonymous_variant	10/11	ENST00000650242.1	NP_000023.2	P22557-1
ALAS2	NM_001037968.4 linkuse as main transcript	c.1524C>T	p.Ser508Ser	synonymous_variant	10/11		NP_001033057.1	P22557-4
ALAS2	NM_001037967.4 linkuse as main transcript	c.1452C>T	p.Ser484Ser	synonymous_variant	9/10		NP_001033056.1	P22557-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ALAS2	ENST00000650242.1 linkuse as main transcript	c.1563C>T	p.Ser521Ser	synonymous_variant	10/11		NM_000032.5	ENSP00000497236.1	P22557-1
ALAS2	ENST00000396198.7 linkuse as main transcript	c.1524C>T	p.Ser508Ser	synonymous_variant	10/11	5		ENSP00000379501.3	P22557-4
ALAS2	ENST00000335854.8 linkuse as main transcript	c.1452C>T	p.Ser484Ser	synonymous_variant	9/10	2		ENSP00000337131.4	P22557-2
ALAS2	ENST00000498636.1 linkuse as main transcript	c.726+1224C>T		intron_variant		3		ENSP00000495662.1	A0A2R8Y6N3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000274

AC:

AN:

182639

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67187

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1097899

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363263

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

Cov.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: 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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 28, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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