12-110281775-C-T

Position:

chr12-110281775-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_170665.4(ATP2A2):c.-15C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,485,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

ATP2A2
NM_170665.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.07

Variant links:

Genes affected

ATP2A2 (HGNC:812): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of the skeletal muscle. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol into the sarcoplasmic reticulum lumen, and is involved in regulation of the contraction/relaxation cycle. Mutations in this gene cause Darier-White disease, also known as keratosis follicularis, an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and abnormal keratinization. Other types of mutations in this gene have been associated with various forms of muscular dystrophies. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]

ATP2A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 12-110281775-C-T is Benign according to our data. Variant chr12-110281775-C-T is described in ClinVar as [Benign]. Clinvar id is 307157.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 56 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2A2	NM_170665.4 linkuse as main transcript	c.-15C>T		5_prime_UTR_premature_start_codon_gain_variant	1/20	ENST00000539276.7	NP_733765.1	P16615-1A0A0S2Z3L2
ATP2A2	NM_170665.4 linkuse as main transcript	c.-15C>T		5_prime_UTR_variant	1/20	ENST00000539276.7	NP_733765.1	P16615-1A0A0S2Z3L2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2A2	ENST00000539276.7 linkuse as main transcript	c.-15C>T		5_prime_UTR_premature_start_codon_gain_variant	1/20	1	NM_170665.4	ENSP00000440045.2		P16615-1
ATP2A2	ENST00000539276.7 linkuse as main transcript	c.-15C>T		5_prime_UTR_variant	1/20	1	NM_170665.4	ENSP00000440045.2		P16615-1

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000337

AC:

AN:

112596

Hom.:

AF XY:

0.000263

AC XY:

AN XY:

60910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000179

Gnomad ASJ exome

AF:

0.00206

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000451

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.000220

AC:

294

AN:

1333648

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

141

AN XY:

657260

show subpopulations

Gnomad4 AFR exome

AF:

0.0000367

Gnomad4 AMR exome

AF:

0.0000720

Gnomad4 ASJ exome

AF:

0.00280

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000208

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000368

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000507

Hom.:

Bravo

AF:

0.000363

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Keratosis follicularis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over