Variant rs2288602 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.1107+33A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,607,840 control chromosomes in the GnomAD database, including 326,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 23142 hom., cov: 33)

Exomes 𝑓: 0.64 ( 303017 hom. )

Consequence

ACTN2
NM_001103.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.494

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-236739565-A-C is Benign according to our data. Variant chr1-236739565-A-C is described in ClinVar as [Benign]. Clinvar id is 671062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ACTN2	NM_001103.4 linkuse as main transcript	c.1107+33A>C	intron_variant	ENST00000366578.6
ACTN2	NM_001278343.2 linkuse as main transcript	c.1107+33A>C	intron_variant
ACTN2	NR_184402.1 linkuse as main transcript	n.1479+33A>C	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTN2	ENST00000366578.6 linkuse as main transcript	c.1107+33A>C		intron_variant		1	NM_001103.4	A1	P35609-1

Frequencies

GnomAD3 genomes

AF:

0.511

AC:

77757

AN:

152034

Hom.:

23143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.536

Gnomad FIN

AF:

0.695

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.524

GnomAD3 exomes

AF:

0.580

AC:

137831

AN:

237546

Hom.:

41861

AF XY:

0.591

AC XY:

76011

AN XY:

128588

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.477

Gnomad ASJ exome

AF:

0.629

Gnomad EAS exome

AF:

0.507

Gnomad SAS exome

AF:

0.544

Gnomad FIN exome

AF:

0.687

Gnomad NFE exome

AF:

0.666

Gnomad OTH exome

AF:

0.606

GnomAD4 exome

AF:

0.639

AC:

929464

AN:

1455690

Hom.:

303017

Cov.:

AF XY:

0.638

AC XY:

461454

AN XY:

723692

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.475

Gnomad4 ASJ exome

AF:

0.624

Gnomad4 EAS exome

AF:

0.528

Gnomad4 SAS exome

AF:

0.550

Gnomad4 FIN exome

AF:

0.691

Gnomad4 NFE exome

AF:

0.670

Gnomad4 OTH exome

AF:

0.603

GnomAD4 genome

AF:

0.511

AC:

77767

AN:

152150

Hom.:

23142

Cov.:

AF XY:

0.513

AC XY:

38140

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.629

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.536

Gnomad4 FIN

AF:

0.695

Gnomad4 NFE

AF:

0.670

Gnomad4 OTH

AF:

0.526

Alfa

AF:

0.599

Hom.:

5394

Bravo

AF:

0.479

Asia WGS

AF:

0.473

AC:

1650

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	-	- -

Myopathy, congenital, with structured cores and z-line abnormalities

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

-0.88

CADD

Benign

1.7

DANN

Benign

0.66

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