rs2736911

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP6_Strong

The NM_001099667.3(ARMS2):c.112C>T (p.Arg38*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant is predicted to lead to nonsense-mediated mRNA decay (NMD). The variant allele was found at a cumulative frequency of 0.145 (AC=233,876) in the gnomAD database across 1,613,820 control chromosomes, including 18,056 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.181. In-silico predictor (BayesDel (addAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1497 hom., cov: 31)

Exomes 𝑓: 0.15 ( 16559 hom. )

Consequence

ARMS2
NM_001099667.3 stop_gained

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.417

Publications

70 publications found

Variant links:

Genes affected

ARMS2 (HGNC:32685): (age-related maculopathy susceptibility 2) This gene encodes a small secreted protein specific to primates. This protein is a component of the choroidal extracellular matrix of the eye. Mutations in this gene are associated with age-related macular degeneration. [provided by RefSeq, Sep 2017]

ARMS2 links:

HTRA1-AS1 (HGNC:58122):

HTRA1-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001099667.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.1811 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001099667.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMS2	NM_001099667.3	MANE Select	c.112C>T	p.Arg38*	stop_gained	Exon 1 of 2	NP_001093137.1	P0C7Q2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARMS2	ENST00000528446.1	TSL:1 MANE Select	c.112C>T	p.Arg38*	stop_gained	Exon 1 of 2	ENSP00000436682.1	P0C7Q2
HTRA1-AS1	ENST00000647969.1		n.182+3656G>A		intron	N/A
HTRA1-AS1	ENST00000650300.1		n.1852+3656G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19959

AN:

152014

Hom.:

1494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0749

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.0682

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.137

GnomAD2 exomes

AF:

0.131

AC:

32700

AN:

249226

AF XY:

0.130

show subpopulations

Gnomad AFR exome

AF:

0.0709

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.155

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.146

AC:

213900

AN:

1461688

Hom.:

16559

Cov.:

AF XY:

0.144

AC XY:

104970

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.0705

AC:

2360

AN:

33480

American (AMR)

AF:

0.111

AC:

4943

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

3390

AN:

26136

East Asian (EAS)

AF:

0.185

AC:

7328

AN:

39700

South Asian (SAS)

AF:

0.0690

AC:

5954

AN:

86258

European-Finnish (FIN)

AF:

0.162

AC:

8637

AN:

53402

Middle Eastern (MID)

AF:

0.0669

AC:

386

AN:

5768

European-Non Finnish (NFE)

AF:

0.155

AC:

172613

AN:

1111846

Other (OTH)

AF:

0.137

AC:

8289

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

11121

22242

33364

44485

55606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5998

11996

17994

23992

29990

<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:

0.131

AC:

19976

AN:

152132

Hom.:

1497

Cov.:

AF XY:

0.130

AC XY:

9658

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0753

AC:

3126

AN:

41504

American (AMR)

AF:

0.132

AC:

2017

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

472

AN:

3472

East Asian (EAS)

AF:

0.165

AC:

853

AN:

5164

South Asian (SAS)

AF:

0.0680

AC:

328

AN:

4822

European-Finnish (FIN)

AF:

0.171

AC:

1804

AN:

10572

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10959

AN:

67992

Other (OTH)

AF:

0.136

AC:

287

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

864

1728

2591

3455

4319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.137

Hom.:

1667

Bravo

AF:

0.125

Asia WGS

AF:

0.106

AC:

369

AN:

3478

EpiCase

AF:

0.151

EpiControl

AF:

0.147

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.221

AC:

27099

AN:

122754

Turkish Variome

AF:

0.0888

AC:

597

AN:

6720

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.143

AC:

1279

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.146

AC:

342

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Age related macular degeneration 8 (1)

ARMS2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Benign

0.95

Eigen

Benign

-0.63

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0040

PhyloP100

-0.42

PromoterAI

-0.028

Neutral

(source)

Mutation Taster

=192/8

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over