dbSNP rs17610181: NACA2:p.Arg197* (chr17-61590592-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_199290.4(NACA2):c.589C>T(p.Arg197*) variant causes a stop gained change. The variant allele was found at a frequency of 0.151 in 1,613,650 control chromosomes in the GnomAD database, including 20,131 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1436 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18695 hom. )

Consequence

NACA2
NM_199290.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.26

Publications

34 publications found

Variant links:

Genes affected

NACA2 (HGNC:23290): (nascent polypeptide associated complex subunit alpha 2) Predicted to enable unfolded protein binding activity. Predicted to be involved in protein targeting to membrane. Predicted to be located in nucleus. Predicted to be part of nascent polypeptide-associated complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NACA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NACA2	NM_199290.4 link	c.589C>T	p.Arg197*	stop_gained	Exon 1 of 1	ENST00000521764.3	NP_954984.1	Q9H009

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NACA2	ENST00000521764.3 link	c.589C>T	p.Arg197*	stop_gained	Exon 1 of 1	6	NM_199290.4	ENSP00000427802.1		Q9H009

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19545

AN:

151982

Hom.:

1441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0692

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.154

GnomAD2 exomes

AF:

0.155

AC:

38964

AN:

251482

AF XY:

0.163

show subpopulations

Gnomad AFR exome

AF:

0.0683

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.154

AC:

224803

AN:

1461548

Hom.:

18695

Cov.:

AF XY:

0.158

AC XY:

114891

AN XY:

727088

show subpopulations

African (AFR)

AF:

0.0660

AC:

2211

AN:

33480

American (AMR)

AF:

0.104

AC:

4653

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

4706

AN:

26134

East Asian (EAS)

AF:

0.163

AC:

6454

AN:

39700

South Asian (SAS)

AF:

0.272

AC:

23462

AN:

86240

European-Finnish (FIN)

AF:

0.118

AC:

6302

AN:

53418

Middle Eastern (MID)

AF:

0.182

AC:

1047

AN:

5768

European-Non Finnish (NFE)

AF:

0.150

AC:

166289

AN:

1111696

Other (OTH)

AF:

0.160

AC:

9679

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

11494

22988

34483

45977

57471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6088

12176

18264

24352

30440

<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:

0.128

AC:

19540

AN:

152102

Hom.:

1436

Cov.:

AF XY:

0.130

AC XY:

9671

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0690

AC:

2865

AN:

41494

American (AMR)

AF:

0.130

AC:

1993

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

581

AN:

3468

East Asian (EAS)

AF:

0.185

AC:

959

AN:

5172

South Asian (SAS)

AF:

0.278

AC:

1339

AN:

4820

European-Finnish (FIN)

AF:

0.115

AC:

1216

AN:

10578

Middle Eastern (MID)

AF:

0.182

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.149

AC:

10116

AN:

67972

Other (OTH)

AF:

0.155

AC:

327

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

880

1760

2639

3519

4399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.125

Hom.:

1039

Bravo

AF:

0.126

TwinsUK

AF:

0.162

AC:

599

ALSPAC

AF:

0.155

AC:

596

ESP6500AA

AF:

0.0747

AC:

329

ESP6500EA

AF:

0.145

AC:

1249

ExAC

AF:

0.156

AC:

18980

Asia WGS

AF:

0.229

AC:

795

AN:

3478

EpiCase

AF:

0.160

EpiControl

AF:

0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.53

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.54

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.54

PhyloP100

5.3

Vest4

0.056

GERP RS

-0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=144/56

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over