10-122456893-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001099667.3(ARMS2):c.298-14_298-13insG variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,542,698 control chromosomes in the GnomAD database, including 60 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (31 hom.)
• Consequence: ARMS2 NM_001099667.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.213

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.

• BP6: Variant 10-122456893-T-TG is Benign according to our data. Variant chr10-122456893-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 299030.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1802/152134) while in subpopulation AFR AF= 0.0397 (1645/41460). AF 95% confidence interval is 0.0381. There are 29 homozygotes in gnomad4. There are 849 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMS2	NM_001099667.3	c.298-14_298-13insG		splice_polypyrimidine_tract_variant, intron_variant		ENST00000528446.1
LOC105378525	XR_946382.3	n.1874+1601_1874+1602insC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMS2	ENST00000528446.1	c.298-14_298-13insG		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001099667.3	P1
	ENST00000650300.1	n.1852+1601_1852+1602insC		intron_variant, non_coding_transcript_variant
	ENST00000647969.1	n.182+1601_182+1602insC		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1796 AN: 152016 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00577

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00748

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00347 AC: 521 AN: 150120 Hom.: 10 AF XY: 0.00358 AC XY: 285 AN XY: 79512

Gnomad AFR exome AF: 0.0368

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00730

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000334

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00191 AC: 2657 AN: 1390564 Hom.: 31 Cov.: 33 AF XY: 0.00201 AC XY: 1379 AN XY: 685728

Gnomad4 AFR exome AF: 0.0428

Gnomad4 AMR exome AF: 0.00285

Gnomad4 ASJ exome AF: 0.0000402

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00822

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000296

Gnomad4 OTH exome AF: 0.00401

GnomAD4 genome AF: 0.0118 AC: 1802 AN: 152134 Hom.: 29 Cov.: 32 AF XY: 0.0114 AC XY: 849 AN XY: 74368

Gnomad4 AFR AF: 0.0397

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00748

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.000863 Hom.: 0

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Macular degeneration Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

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: rs529644268; hg19: chr10-124216409;