chr16-84368651-A-T

Position:

• chr16-84368651-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014861.4(ATP2C2):​c.36A>T​(p.Lys12Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATP2C2 NM_014861.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.686

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]

ACMG classification

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.36A>T	p.Lys12Asn	missense_variant	1/27	ENST00000262429.9
ATP2C2	NM_001286527.3	c.36A>T	p.Lys12Asn	missense_variant	1/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C2	ENST00000262429.9	c.36A>T	p.Lys12Asn	missense_variant	1/27	1	NM_014861.4	P1
ATP2C2	ENST00000416219.6	c.36A>T	p.Lys12Asn	missense_variant	1/28	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2024

The c.36A>T (p.K12N) alteration is located in exon 1 (coding exon 1) of the ATP2C2 gene. This alteration results from a A to T substitution at nucleotide position 36, causing the lysine (K) at amino acid position 12 to be replaced by an asparagine (N). 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	0.13
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.73	T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	0.99	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.57	N;N
REVEL	Benign	0.29
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.067	B;.
Vest4		0.52
MutPred		0.42		Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);
MVP		0.31
ClinPred		0.58	D
GERP RS		-2.4
Varity_R		0.19
gMVP		0.46

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: chr16-84402257;