rs552471202

Variant names:

• chr1-236686571-GCGCCCGCCGCCCGC-G
• rs552471202
• NM_001103.4:c.-91_-78delCGCCGCCCGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr1-236686571-GCGCCCGCCGCCCGC-G
• chr1-236686571-GCGCCCGCCGCCCGC-GCGCCCGC
• chr1-236686571-GCGCCCGCCGCCCGC-GCGCCCGCCGCCCGCCGCCCGC
• chr1-236686571-GCGCCCGCCGCCCGC-GCGCCCGCCGCCCGCCGCCCGCCGCCCGC
• chr1-236686571-GCGCCCGCCGCCCGC-GCGCCCGCCGCCCGCCGCCCGCCGCCCGCCGCCCGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001103.4(ACTN2):​c.-91_-78delCGCCGCCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000602 in 1,162,038 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: ACTN2 NM_001103.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• ACTN2-related cardiac and skeletal myopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• myopathy, congenital, with structured cores and z-line abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dilated cardiomyopathy 1AA

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• intrinsic cardiomyopathy

  Inheritance: AD Classification: MODERATE Submitted by: Laboratory for Molecular Medicine
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• heart conduction disease

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
• myopathy, distal, 6, adult-onset, autosomal dominant

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Broad Center for Mendelian Genomics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001103.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN2	NM_001103.4	MANE Select	c.-91_-78delCGCCGCCCGCCGCC		5_prime_UTR	Exon 1 of 21	NP_001094.1	P35609-1
	ACTN2	NM_001278343.2		c.-91_-78delCGCCGCCCGCCGCC		5_prime_UTR	Exon 1 of 21	NP_001265272.1	P35609-2
	ACTN2	NR_184402.1		n.85_98delCGCCGCCCGCCGCC		non_coding_transcript_exon	Exon 1 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN2	ENST00000366578.6	TSL:1 MANE Select	c.-91_-78delCGCCGCCCGCCGCC		5_prime_UTR	Exon 1 of 21	ENSP00000355537.4	P35609-1
	ACTN2	ENST00000542672.7	TSL:1	c.-91_-78delCGCCGCCCGCCGCC		5_prime_UTR	Exon 1 of 21	ENSP00000443495.1	P35609-2
	ACTN2	ENST00000879537.1		c.-91_-78delCGCCGCCCGCCGCC		5_prime_UTR	Exon 1 of 22	ENSP00000549596.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000602 AC: 7 AN: 1162038 Hom.: 0 AF XY: 0.00000529 AC XY: 3 AN XY: 567240

African (AFR) AF: 0.00 AC: 0 AN: 21744

American (AMR) AF: 0.00 AC: 0 AN: 8804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14754

East Asian (EAS) AF: 0.000163 AC: 4 AN: 24486

South Asian (SAS) AF: 0.00 AC: 0 AN: 45812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3164

European-Non Finnish (NFE) AF: 0.00000313 AC: 3 AN: 959578

Other (OTH) AF: 0.00 AC: 0 AN: 46412

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs552471202; hg19: chr1-236849871;