16-84405221-G-C

Variant names:

• chr16-84405221-G-C
• NM_014861.4:c.304G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014861.4(ATP2C2):​c.304G>C​(p.Val102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ATP2C2 NM_014861.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22056276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2C2	NM_014861.4	c.304G>C	p.Val102Leu	missense_variant	Exon 3 of 27	ENST00000262429.9	NP_055676.3
ATP2C2	NM_001286527.3	c.304G>C	p.Val102Leu	missense_variant	Exon 3 of 28		NP_001273456.2
ATP2C2	XM_011523486.3	c.235G>C	p.Val79Leu	missense_variant	Exon 3 of 28		XP_011521788.1
ATP2C2	XM_047434994.1	c.235G>C	p.Val79Leu	missense_variant	Exon 3 of 27		XP_047290950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2C2	ENST00000262429.9	c.304G>C	p.Val102Leu	missense_variant	Exon 3 of 27	1	NM_014861.4	ENSP00000262429.4
ATP2C2	ENST00000416219.6	c.304G>C	p.Val102Leu	missense_variant	Exon 3 of 28	1		ENSP00000397925.2
ATP2C2	ENST00000565631.5	n.795G>C		non_coding_transcript_exon_variant	Exon 1 of 25	2
ATP2C2	ENST00000569207.5	n.1G>C		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000456595.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461714 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	1.2
DANN	Benign	0.14
DEOGEN2	Benign	0.0055	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.31	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.57	N;N
REVEL	Benign	0.14
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.54
MutPred		0.37		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.28
ClinPred		0.0096	T
GERP RS		2.0
Varity_R		0.031
gMVP		0.28

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: chr16-84438827;