16-28878376-C-CT

Variant names:

• chr16-28878376-C-CT
• rs201017113
• ENST00000691192.2:n.1560dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000691192.2(ATP2A1-AS1):​n.1560dupA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7930 hom., cov: 20)
  • Exomes 𝑓: 0.33 (17226 hom.)
• Consequence: ATP2A1-AS1 ENST00000691192.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.42
• Publications: 3 publications found

Genes affected

ATP2A1-AS1 (HGNC:51370): (ATP2A1 antisense RNA 1)

ATP2A1 (HGNC:811): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Oct 2013]

ATP2A1 Gene-Disease associations (from GenCC):

• Brody myopathy

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-28878376-C-CT is Benign according to our data. Variant chr16-28878376-C-CT is described in ClinVar as [Benign]. Clinvar id is 1291696.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A1	NM_004320.6	c.-296_-295insT		upstream_gene_variant		ENST00000395503.9	NP_004311.1
ATP2A1	NM_173201.5	c.-296_-295insT		upstream_gene_variant			NP_775293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A1-AS1	ENST00000691192.2	n.1560dupA		non_coding_transcript_exon_variant	Exon 1 of 1
ATP2A1	ENST00000395503.9	c.-296_-295insT		upstream_gene_variant		1	NM_004320.6	ENSP00000378879.5
ATP2A1	ENST00000357084.7	c.-296_-295insT		upstream_gene_variant		2		ENSP00000349595.3

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43115 AN: 149682 Hom.: 7918 Cov.: 20

Gnomad AFR AF: 0.0761

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.330 AC: 92424 AN: 280324 Hom.: 17226 Cov.: 0 AF XY: 0.320 AC XY: 47930 AN XY: 149758

African (AFR) AF: 0.0634 AC: 526 AN: 8294

American (AMR) AF: 0.438 AC: 5825 AN: 13292

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 2042 AN: 8010

East Asian (EAS) AF: 0.114 AC: 1778 AN: 15588

South Asian (SAS) AF: 0.210 AC: 8560 AN: 40838

European-Finnish (FIN) AF: 0.412 AC: 6143 AN: 14926

Middle Eastern (MID) AF: 0.206 AC: 236 AN: 1146

European-Non Finnish (NFE) AF: 0.383 AC: 62325 AN: 162716

Other (OTH) AF: 0.322 AC: 4989 AN: 15514

GnomAD4 genome AF: 0.288 AC: 43136 AN: 149768 Hom.: 7930 Cov.: 20 AF XY: 0.287 AC XY: 21027 AN XY: 73230

African (AFR) AF: 0.0759 AC: 2989 AN: 39392

American (AMR) AF: 0.385 AC: 5862 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3468

East Asian (EAS) AF: 0.111 AC: 574 AN: 5152

South Asian (SAS) AF: 0.202 AC: 971 AN: 4810

European-Finnish (FIN) AF: 0.421 AC: 4440 AN: 10536

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26517 AN: 67888

Other (OTH) AF: 0.272 AC: 571 AN: 2096

Alfa AF: 0.334 Hom.: 1027

Asia WGS AF: 0.214 AC: 736 AN: 3442

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

Splicing

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

Other links and lift over

dbSNP: rs201017113; hg19: chr16-28889697; COSMIC: COSV59463024;