NM_014861.4:c.2333+112T>C

Variant names:

• chr16-84459498-T-C
• rs746162693
• NM_014861.4:c.2333+112T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014861.4(ATP2C2):​c.2333+112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 35)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ATP2C2 NM_014861.4 intron
• Scores: Splicing: ADA: 0.00006260
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• 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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.2333+112T>C		intron	N/A	NP_055676.3	O75185-1
	ATP2C2	NM_001286527.3		c.2334-8T>C		splice_region intron	N/A	NP_001273456.2	O75185-3
	ATP2C2	NM_001291454.2		c.1880+112T>C		intron	N/A	NP_001278383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C2	ENST00000262429.9	TSL:1 MANE Select	c.2333+112T>C		intron	N/A	ENSP00000262429.4	O75185-1
	ATP2C2	ENST00000416219.7	TSL:1	c.2334-8T>C		splice_region intron	N/A	ENSP00000397925.2
	ATP2C2-AS1	ENST00000565700.1	TSL:1	n.2759A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1430540 Hom.: 0 Cov.: 38 AF XY: 0.00000141 AC XY: 1 AN XY: 710158

African (AFR) AF: 0.00 AC: 0 AN: 33022

American (AMR) AF: 0.00 AC: 0 AN: 40426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25656

East Asian (EAS) AF: 0.00 AC: 0 AN: 38616

South Asian (SAS) AF: 0.00 AC: 0 AN: 83786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1099088

Other (OTH) AF: 0.00 AC: 0 AN: 59436

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		-0.13

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000063
dbscSNV1_RF	Benign	0.0080
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: rs746162693; hg19: chr16-84493104;