10-122454839-C-T

Position:

chr10-122454839-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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 allele was found at a frequency of 0.145 in 1,613,820 control chromosomes in the GnomAD database, including 18,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

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

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:

ENSG00000285955 (HGNC:):

ENSG00000285955 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-122454839-C-T is Benign according to our data. Variant chr10-122454839-C-T is described in ClinVar as [Benign]. Clinvar id is 299029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMS2	NM_001099667.3 linkuse as main transcript	c.112C>T	p.Arg38*	stop_gained	1/2	ENST00000528446.1	NP_001093137.1	P0C7Q2
LOC105378525	XR_946382.3 linkuse as main transcript	n.1874+3656G>A		intron_variant
LOC105378525	XR_946383.3 linkuse as main transcript	n.1852+3656G>A		intron_variant
LOC105378525	XR_946384.3 linkuse as main transcript	n.1601+3656G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARMS2	ENST00000528446.1 linkuse as main transcript	c.112C>T	p.Arg38*	stop_gained	1/2	1	NM_001099667.3	ENSP00000436682.1	P0C7Q2
ENSG00000285955	ENST00000647969.1 linkuse as main transcript	n.182+3656G>A		intron_variant
ENSG00000285955	ENST00000650300.1 linkuse as main transcript	n.1852+3656G>A		intron_variant

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

GnomAD3 exomes

AF:

0.131

AC:

32700

AN:

249226

Hom.:

2409

AF XY:

0.130

AC XY:

17629

AN XY:

135210

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 SAS exome

AF:

0.0689

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

Gnomad4 AFR exome

AF:

0.0705

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.185

Gnomad4 SAS exome

AF:

0.0690

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.131

AC:

19976

AN:

152132

Hom.:

1497

Cov.:

AF XY:

0.130

AC XY:

9658

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0753

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.0680

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.134

Hom.:

1253

Bravo

AF:

0.125

TwinsUK

AF:

0.150

AC:

557

ALSPAC

AF:

0.158

AC:

608

ESP6500AA

AF:

0.0709

AC:

288

ESP6500EA

AF:

0.152

AC:

1274

ExAC

AF:

0.131

AC:

15813

Asia WGS

AF:

0.106

AC:

369

AN:

3478

EpiCase

AF:

0.151

EpiControl

AF:

0.147

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Age related macular degeneration 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

ARMS2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 04, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Benign

0.95

Eigen

Benign

-0.63

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0040

Vest4

0.66

GERP RS

-2.2

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