chr16-84408489-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_014861.4(ATP2C2):c.412G>A(p.Ala138Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,612,442 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0036 ( 3 hom., cov: 31)
Exomes 𝑓: 0.0038 ( 28 hom. )
Consequence
ATP2C2
NM_014861.4 missense
NM_014861.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: -0.240
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009264618).
BP6
?
Variant 16-84408489-G-A is Benign according to our data. Variant chr16-84408489-G-A is described in ClinVar as [Benign]. Clinvar id is 779452.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00384 (5603/1460446) while in subpopulation AMR AF= 0.0178 (798/44718). AF 95% confidence interval is 0.0168. There are 28 homozygotes in gnomad4_exome. There are 2604 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2C2 | NM_014861.4 | c.412G>A | p.Ala138Thr | missense_variant | 4/27 | ENST00000262429.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2C2 | ENST00000262429.9 | c.412G>A | p.Ala138Thr | missense_variant | 4/27 | 1 | NM_014861.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00354 AC: 538AN: 151878Hom.: 3 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00589 AC: 1459AN: 247790Hom.: 10 AF XY: 0.00499 AC XY: 672AN XY: 134580
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GnomAD4 exome AF: 0.00384 AC: 5603AN: 1460446Hom.: 28 Cov.: 31 AF XY: 0.00358 AC XY: 2604AN XY: 726528
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GnomAD4 genome ? AF: 0.00357 AC: 543AN: 151996Hom.: 3 Cov.: 31 AF XY: 0.00342 AC XY: 254AN XY: 74282
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722
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
ClinPred
T
GERP RS
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gMVP
Splicing
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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