rs563811998

Variant names:

• chr12-110281801-G-A
• NM_170665.4:c.12G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-110281801-G-A
• chr12-110281801-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_170665.4(ATP2A2):​c.12G>A​(p.Ala4Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,372,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ATP2A2 NM_170665.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642

Genes affected

ATP2A2 (HGNC:812): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of the skeletal muscle. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol into the sarcoplasmic reticulum lumen, and is involved in regulation of the contraction/relaxation cycle. Mutations in this gene cause Darier-White disease, also known as keratosis follicularis, an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal keratinization. Other types of mutations in this gene have been associated with various forms of muscular dystrophies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=0.642 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A2	NM_170665.4	c.12G>A	p.Ala4Ala	synonymous_variant	Exon 1 of 20	ENST00000539276.7	NP_733765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A2	ENST00000539276.7	c.12G>A	p.Ala4Ala	synonymous_variant	Exon 1 of 20	1	NM_170665.4	ENSP00000440045.2
ATP2A2	ENST00000308664.10	c.12G>A	p.Ala4Ala	synonymous_variant	Exon 1 of 21	1		ENSP00000311186.6
ATP2A2	ENST00000552636.2	c.-257-803G>A		intron_variant	Intron 1 of 4	4		ENSP00000447406.2
ATP2A2	ENST00000377685.9	n.12G>A		non_coding_transcript_exon_variant	Exon 1 of 20	5		ENSP00000366913.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1372446 Hom.: 0 Cov.: 30 AF XY: 0.00000295 AC XY: 2 AN XY: 677952

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-110719606;