1-236686571-GCGCCCGCCGCCCGC-GCGCCCGCCGCCCGCCGCCCGCCGCCCGC

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001103.4(ACTN2):​c.-91_-78dupCGCCGCCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 150,826 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000027 (0 hom., cov: 30)
• Consequence: ACTN2 NM_001103.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTN2	NM_001103.4	c.-91_-78dupCGCCGCCCGCCGCC		5_prime_UTR_variant	Exon 1 of 21	ENST00000366578.6	NP_001094.1
ACTN2	NM_001278343.2	c.-91_-78dupCGCCGCCCGCCGCC		5_prime_UTR_variant	Exon 1 of 21		NP_001265272.1
ACTN2	NR_184402.1	n.85_98dupCGCCGCCCGCCGCC		non_coding_transcript_exon_variant	Exon 1 of 23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTN2	ENST00000366578	c.-91_-78dupCGCCGCCCGCCGCC		5_prime_UTR_variant	Exon 1 of 21	1	NM_001103.4	ENSP00000355537.4

Frequencies

GnomAD3 genomes AF: 0.0000265 AC: 4 AN: 150826 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 20

GnomAD4 genome AF: 0.0000265 AC: 4 AN: 150826 Hom.: 0 Cov.: 30 AF XY: 0.0000407 AC XY: 3 AN XY: 73654

Gnomad4 AFR AF: 0.0000730

Gnomad4 AMR AF: 0.0000662

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs552471202; hg19: chr1-236849871;