rs550921485

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002143.3(HPCA):c.568G>A(p.Ala190Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000203 in 1,570,368 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 4 hom. )

Consequence

HPCA
NM_002143.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: 4.03

Publications

4 publications found

Variant links:

Genes affected

HPCA (HGNC:5144): (hippocalcin) The protein encoded by this gene is a member of neuron-specific calcium-binding proteins family found in the retina and brain. This protein is associated with the plasma membrane. It has similarities to proteins located in the photoreceptor cells that regulate photosignal transduction in a calcium-sensitive manner. This protein displays recoverin activity and a calcium-dependent inhibition of rhodopsin kinase. It is identical to the rat and mouse hippocalcin proteins and thought to play an important role in neurons of the central nervous system in a number of species. [provided by RefSeq, Jul 2008]

HPCA Gene-Disease associations (from GenCC):

torsion dystonia 2
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

HPCA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005412847).

BP6

Variant 1-32893848-G-A is Benign according to our data. Variant chr1-32893848-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 190120.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
HPCA	NM_002143.3 link	c.568G>A	p.Ala190Thr	missense_variant	Exon 4 of 4	ENST00000373467.4	NP_002134.2
HPCA	XM_005270792.4 link	c.568G>A	p.Ala190Thr	missense_variant	Exon 4 of 4		XP_005270849.1
HPCA	XM_017001118.3 link	c.568G>A	p.Ala190Thr	missense_variant	Exon 4 of 4		XP_016856607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPCA	ENST00000373467.4 link	c.568G>A	p.Ala190Thr	missense_variant	Exon 4 of 4	1	NM_002143.3	ENSP00000362566.3

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000495

AC:

AN:

179930

AF XY:

0.000658

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000226

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000408

GnomAD4 exome

AF:

0.000214

AC:

303

AN:

1418084

Hom.:

Cov.:

AF XY:

0.000288

AC XY:

202

AN XY:

701576

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32102

American (AMR)

AF:

0.00

AC:

AN:

37880

Ashkenazi Jewish (ASJ)

AF:

0.000118

AC:

AN:

25432

East Asian (EAS)

AF:

0.00

AC:

AN:

36746

South Asian (SAS)

AF:

0.00352

AC:

284

AN:

80600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

9.17e-7

AC:

AN:

1090438

Other (OTH)

AF:

0.000255

AC:

AN:

58886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00269

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000868

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.00

AC:

ExAC

AF:

0.000345

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Torsion dystonia 2

Pathogenic:1

Apr 02, 2015

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

not provided

Benign:1

Jul 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.18

Eigen_PC

Benign

0.018

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.015

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

PhyloP100

4.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.28

Sift

Benign

0.18

Sift4G

Benign

0.098

Vest4

0.12

ClinPred

0.071

GERP RS

3.5

Varity_R

0.41

gMVP

0.79

Mutation Taster

=61/39

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over