10-122456978-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001099667.3(ARMS2):c.*45T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000781 in 1,551,140 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (8 hom.)
• Consequence: ARMS2 NM_001099667.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.37

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-122456978-T-G is Benign according to our data. Variant chr10-122456978-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 879637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMS2	NM_001099667.3	c.*45T>G		3_prime_UTR_variant	2/2	ENST00000528446.1
LOC105378525	XR_946382.3	n.1874+1517A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMS2	ENST00000528446.1	c.*45T>G		3_prime_UTR_variant	2/2	1	NM_001099667.3	P1
	ENST00000650300.1	n.1852+1517A>C		intron_variant, non_coding_transcript_variant
	ENST00000647969.1	n.182+1517A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00388 AC: 590 AN: 152160 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000976 AC: 148 AN: 151642 Hom.: 1 AF XY: 0.000870 AC XY: 70 AN XY: 80432

Gnomad AFR exome AF: 0.0136

Gnomad AMR exome AF: 0.00106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000177

Gnomad FIN exome AF: 0.0000655

Gnomad NFE exome AF: 0.000122

Gnomad OTH exome AF: 0.000466

GnomAD4 exome AF: 0.000437 AC: 611 AN: 1398862 Hom.: 8 Cov.: 32 AF XY: 0.000422 AC XY: 291 AN XY: 689896

Gnomad4 AFR exome AF: 0.0136

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000759

Gnomad4 FIN exome AF: 0.0000609

Gnomad4 NFE exome AF: 0.0000501

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.00395 AC: 601 AN: 152278 Hom.: 3 Cov.: 32 AF XY: 0.00376 AC XY: 280 AN XY: 74466

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00167 Hom.: 1

Bravo AF: 0.00435

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Age related macular degeneration 8 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.55
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs150019974; hg19: chr10-124216494;