16-84398538-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014861.4(ATP2C2):c.139A>G(p.Lys47Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ATP2C2
NM_014861.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

Publications

1 publications found

Variant links:

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]

ATP2C2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08535129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4 link	c.139A>G	p.Lys47Glu	missense_variant	Exon 2 of 27	ENST00000262429.9	NP_055676.3	O75185-1
ATP2C2	NM_001286527.3 link	c.139A>G	p.Lys47Glu	missense_variant	Exon 2 of 28		NP_001273456.2	O75185-3
ATP2C2	XM_011523486.3 link	c.70A>G	p.Lys24Glu	missense_variant	Exon 2 of 28		XP_011521788.1
ATP2C2	XM_047434994.1 link	c.70A>G	p.Lys24Glu	missense_variant	Exon 2 of 27		XP_047290950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C2	ENST00000262429.9 link	c.139A>G	p.Lys47Glu	missense_variant	Exon 2 of 27	1	NM_014861.4	ENSP00000262429.4		O75185-1
ATP2C2	ENST00000416219.7 link	c.139A>G	p.Lys47Glu	missense_variant	Exon 2 of 28	1		ENSP00000397925.2		O75185-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461248

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1111772

Other (OTH)

AF:

0.00

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.139A>G (p.K47E) alteration is located in exon 2 (coding exon 2) of the ATP2C2 gene. This alteration results from a A to G substitution at nucleotide position 139, causing the lysine (K) at amino acid position 47 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.033

T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.085

T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.90

L;L

PhyloP100

2.6

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.28

Sift

Benign

0.43

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.077

B;.

Vest4

0.43

MutPred

0.25

Loss of ubiquitination at K47 (P = 0.0141);Loss of ubiquitination at K47 (P = 0.0141);

MVP

0.71

ClinPred

0.53

GERP RS

2.8

Varity_R

0.28

gMVP

0.46

Mutation Taster

=92/8

polymorphism

(source)

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

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16-84398538-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over