rs376292409

Variant names:

• chr16-84459313-A-G
• rs376292409
• NM_014861.4:c.2260A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014861.4(ATP2C2):​c.2260A>G​(p.Asn754Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000155 in 1,614,170 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (2 hom.)
• Consequence: ATP2C2 NM_014861.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.18
• Publications: 0 publications found

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-AS1 (HGNC:53167): (ATP2C2 antisense RNA 1)

ENSG00000305404 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13868907).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014861.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C2	NM_014861.4	MANE Select	c.2260A>G	p.Asn754Asp	missense	Exon 23 of 27	NP_055676.3	O75185-1
	ATP2C2	NM_001286527.3		c.2260A>G	p.Asn754Asp	missense	Exon 23 of 28	NP_001273456.2	O75185-3
	ATP2C2	NM_001291454.2		c.1807A>G	p.Asn603Asp	missense	Exon 20 of 24	NP_001278383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C2	ENST00000262429.9	TSL:1 MANE Select	c.2260A>G	p.Asn754Asp	missense	Exon 23 of 27	ENSP00000262429.4	O75185-1
	ATP2C2	ENST00000416219.7	TSL:1	c.2260A>G	p.Asn754Asp	missense	Exon 23 of 28	ENSP00000397925.2
	ATP2C2-AS1	ENST00000565700.1	TSL:1	n.2944T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000156 AC: 39 AN: 249562 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000156 AC: 228 AN: 1461886 Hom.: 2 Cov.: 37 AF XY: 0.000164 AC XY: 119 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000452 AC: 39 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.000138 AC: 154 AN: 1112010

Other (OTH) AF: 0.000381 AC: 23 AN: 60396

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152284 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74470

African (AFR) AF: 0.0000481 AC: 2 AN: 41562

American (AMR) AF: 0.000589 AC: 9 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000262 Hom.: 0

Bravo AF: 0.000230

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000238 AC: 2

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	0.45	N
PhyloP100		5.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.41
Sift	Benign	0.12	T
Sift4G	Uncertain	0.056	T
Polyphen		0.0010	B
Vest4		0.43
MVP		0.74
ClinPred		0.12	T
GERP RS		1.1
Varity_R		0.13
gMVP		0.58
Mutation Taster		=93/7	polymorphism

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: rs376292409; hg19: chr16-84492919; COSMIC: COSV105103612; COSMIC: COSV105103612;