Variant rs2288600 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_001103.4(ACTN2):c.783+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,605,616 control chromosomes in the GnomAD database, including 18,455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2035 hom., cov: 33)

Exomes 𝑓: 0.15 ( 16420 hom. )

Consequence

ACTN2
NM_001103.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0450

Variant links:

Genes affected

ACTN2 (HGNC:164): (actinin alpha 2) Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

ACTN2 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=-0.86).

BP6

Variant 1-236735742-G-A is Benign according to our data. Variant chr1-236735742-G-A is described in ClinVar as [Benign]. Clinvar id is 177799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ACTN2	NM_001103.4 linkuse as main transcript	c.783+22G>A	intron_variant	ENST00000366578.6	NP_001094.1
ACTN2	NM_001278343.2 linkuse as main transcript	c.783+1224G>A	intron_variant		NP_001265272.1
ACTN2	NR_184402.1 linkuse as main transcript	n.1044+22G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTN2	ENST00000366578.6 linkuse as main transcript	c.783+22G>A		intron_variant		1	NM_001103.4	ENSP00000355537	A1	P35609-1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24446

AN:

152012

Hom.:

2033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.162

AC:

40416

AN:

249642

Hom.:

3391

AF XY:

0.161

AC XY:

21699

AN XY:

134962

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.187

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.147

AC:

213444

AN:

1453486

Hom.:

16420

Cov.:

AF XY:

0.148

AC XY:

106979

AN XY:

723542

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.206

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.161

AC:

24455

AN:

152130

Hom.:

2035

Cov.:

AF XY:

0.163

AC XY:

12099

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.163

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.190

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.142

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.138

Hom.:

2103

Bravo

AF:

0.165

Asia WGS

AF:

0.202

AC:

702

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 16, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.9

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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