16-84415518-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014861.4(ATP2C2):c.551G>A(p.Arg184Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,614,164 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 1 hom. )
Consequence
ATP2C2
NM_014861.4 missense
NM_014861.4 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 8.25
Genes affected
ATP2C2 (HGNC:29103): (ATPase secretory pathway Ca2+ transporting 2) Enables P-type calcium transporter activity and P-type manganese transporter activity. Predicted to be involved in calcium ion transmembrane transport; cellular calcium ion homeostasis; and manganese ion transport. Predicted to act upstream of or within mammary gland epithelium development; positive regulation of calcium ion import; and protein localization to plasma membrane. Predicted to be located in trans-Golgi network membrane. Predicted to be active in Golgi membrane; endoplasmic reticulum; and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2C2 | NM_014861.4 | c.551G>A | p.Arg184Gln | missense_variant | 7/27 | ENST00000262429.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2C2 | ENST00000262429.9 | c.551G>A | p.Arg184Gln | missense_variant | 7/27 | 1 | NM_014861.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152168Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000601 AC: 15AN: 249534Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135388
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461878Hom.: 1 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727240
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74456
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2023 | The c.551G>A (p.R184Q) alteration is located in exon 7 (coding exon 7) of the ATP2C2 gene. This alteration results from a G to A substitution at nucleotide position 551, causing the arginine (R) at amino acid position 184 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Uncertain
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at