Genetic Variant NM_014861.4:c.2226C>T (chr16-84459279-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_014861.4(ATP2C2):c.2226C>T(p.Ser742Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,614,212 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 2 hom. )

Consequence

ATP2C2
NM_014861.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -8.34

Publications

2 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:

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

ATP2C2-AS1 links:

ENSG00000305404 (HGNC:):

ENSG00000305404 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-84459279-C-T is Benign according to our data. Variant chr16-84459279-C-T is described in ClinVar as Benign. ClinVar VariationId is 721014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.34 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2C2	NM_014861.4	MANE Select	c.2226C>T	p.Ser742Ser	synonymous	Exon 23 of 27	NP_055676.3	O75185-1
ATP2C2	NM_001286527.3		c.2226C>T	p.Ser742Ser	synonymous	Exon 23 of 28	NP_001273456.2	O75185-3
ATP2C2	NM_001291454.2		c.1773C>T	p.Ser591Ser	synonymous	Exon 20 of 24	NP_001278383.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2C2	ENST00000262429.9	TSL:1 MANE Select	c.2226C>T	p.Ser742Ser	synonymous	Exon 23 of 27	ENSP00000262429.4	O75185-1
ATP2C2	ENST00000416219.7	TSL:1	c.2226C>T	p.Ser742Ser	synonymous	Exon 23 of 28	ENSP00000397925.2
ATP2C2-AS1	ENST00000565700.1	TSL:1	n.2978G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00165

AC:

251

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00654

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00149

AC:

372

AN:

249524

AF XY:

0.00149

show subpopulations

Gnomad AFR exome

AF:

0.00291

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00912

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000980

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000938

AC:

1371

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000920

AC XY:

669

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00421

AC:

141

AN:

33478

American (AMR)

AF:

0.000537

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.00668

AC:

265

AN:

39700

South Asian (SAS)

AF:

0.000777

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000671

AC:

746

AN:

1112002

Other (OTH)

AF:

0.00116

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

177

266

354

443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00165

AC:

252

AN:

152348

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00332

AC:

138

AN:

41586

American (AMR)

AF:

0.000588

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00655

AC:

AN:

5188

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000794

AC:

AN:

68024

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000793

Hom.:

Bravo

AF:

0.00180

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00136

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.020

(source)

DANN

Benign

0.84

PhyloP100

-8.3

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over