NM_001099667.3:c.297+62_297+63dupTG

Variant names:

• chr10-122455084-G-GGT
• rs61544945
• NM_001099667.3:c.297+62_297+63dupTG

Variant summary

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

The NM_001099667.3(ARMS2):​c.297+62_297+63dupTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 937,644 control chromosomes in the GnomAD database, including 25,076 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4389 hom., cov: 25)
  • Exomes 𝑓: 0.21 (20687 hom.)
• Consequence: ARMS2 NM_001099667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 2 publications found

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]

ENSG00000285955 (HGNC:58122):

ACMG classification

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

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMS2	NM_001099667.3	MANE Select	c.297+62_297+63dupTG		intron	N/A	NP_001093137.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMS2	ENST00000528446.1	TSL:1 MANE Select	c.297+60_297+61insGT		intron	N/A	ENSP00000436682.1
	ENSG00000285955	ENST00000647969.1		n.182+3410_182+3411insAC		intron	N/A
	ENSG00000285955	ENST00000650300.1		n.1852+3410_1852+3411insAC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35665 AN: 151862 Hom.: 4382 Cov.: 25

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.214 AC: 168255 AN: 785664 Hom.: 20687 AF XY: 0.217 AC XY: 87517 AN XY: 402836

African (AFR) AF: 0.220 AC: 4291 AN: 19510

American (AMR) AF: 0.260 AC: 8094 AN: 31118

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 3656 AN: 18998

East Asian (EAS) AF: 0.376 AC: 12267 AN: 32664

South Asian (SAS) AF: 0.304 AC: 18317 AN: 60156

European-Finnish (FIN) AF: 0.230 AC: 8636 AN: 37596

Middle Eastern (MID) AF: 0.191 AC: 824 AN: 4322

European-Non Finnish (NFE) AF: 0.191 AC: 103741 AN: 543814

Other (OTH) AF: 0.225 AC: 8429 AN: 37486

GnomAD4 genome AF: 0.235 AC: 35705 AN: 151980 Hom.: 4389 Cov.: 25 AF XY: 0.238 AC XY: 17651 AN XY: 74304

African (AFR) AF: 0.231 AC: 9582 AN: 41438

American (AMR) AF: 0.233 AC: 3561 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 706 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2118 AN: 5132

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4818

European-Finnish (FIN) AF: 0.235 AC: 2477 AN: 10560

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14904 AN: 67954

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.246 Hom.: 556

Bravo AF: 0.236

Asia WGS AF: 0.369 AC: 1278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.076
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61544945; hg19: chr10-124214600; COSMIC: COSV73307016;