rs1803738

Variant names:

• chr12-110347093-T-A
• rs1803738
• ENST00000313432.5:n.1575T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-110347093-T-A
• chr12-110347093-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000313432.5(ATP2A2):​n.1575T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000359 in 1,113,194 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: 𝑓 0.0000071 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: ATP2A2 ENST00000313432.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

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]

ATP2A2 Gene-Disease associations (from GenCC):

• acrokeratosis verruciformis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Darier disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000313432.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A2	NM_170665.4	MANE Select	c.*623T>A		3_prime_UTR	Exon 20 of 20	NP_733765.1
	ATP2A2	NM_001413013.1		c.*623T>A		3_prime_UTR	Exon 19 of 19	NP_001399942.1
	ATP2A2	NM_001413015.1		c.*623T>A		3_prime_UTR	Exon 20 of 20	NP_001399944.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A2	ENST00000313432.5	TSL:1	n.1575T>A		non_coding_transcript_exon	Exon 2 of 2
	ATP2A2	ENST00000539276.7	TSL:1 MANE Select	c.*623T>A		3_prime_UTR	Exon 20 of 20	ENSP00000440045.2
	ATP2A2	ENST00000308664.10	TSL:1	c.2980+772T>A		intron	N/A	ENSP00000311186.6

Frequencies

GnomAD3 genomes AF: 0.00000713 AC: 1 AN: 140188 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000153

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000308 AC: 3 AN: 973006 Hom.: 0 Cov.: 34 AF XY: 0.00000217 AC XY: 1 AN XY: 460874

African (AFR) AF: 0.00 AC: 0 AN: 19644

American (AMR) AF: 0.00 AC: 0 AN: 7856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8306

East Asian (EAS) AF: 0.00 AC: 0 AN: 9880

South Asian (SAS) AF: 0.00 AC: 0 AN: 41082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2092

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 843284

Other (OTH) AF: 0.00 AC: 0 AN: 34206

GnomAD4 genome AF: 0.00000713 AC: 1 AN: 140188 Hom.: 0 Cov.: 30 AF XY: 0.0000146 AC XY: 1 AN XY: 68288

African (AFR) AF: 0.00 AC: 0 AN: 35460

American (AMR) AF: 0.00 AC: 0 AN: 14446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3320

East Asian (EAS) AF: 0.00 AC: 0 AN: 4606

South Asian (SAS) AF: 0.00 AC: 0 AN: 4122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65564

Other (OTH) AF: 0.00 AC: 0 AN: 1976

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
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.3
DANN	Benign	0.65
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1803738; hg19: chr12-110784898;