chr10-122454932-G-C

Position:

• chr10-122454932-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099667.3(ARMS2):​c.205G>C​(p.Ala69Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARMS2 NM_001099667.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119980395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMS2	NM_001099667.3	c.205G>C	p.Ala69Pro	missense_variant	1/2	ENST00000528446.1	NP_001093137.1
LOC105378525	XR_946382.3	n.1874+3563C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMS2	ENST00000528446.1	c.205G>C	p.Ala69Pro	missense_variant	1/2	1	NM_001099667.3	ENSP00000436682	P1
	ENST00000650300.1	n.1852+3563C>G		intron_variant, non_coding_transcript_variant
	ENST00000647969.1	n.182+3563C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.094
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.45	B
Vest4		0.32
MutPred		0.40		Loss of helix (P = 0.0041);
MVP		0.048
MPC		1.5
ClinPred		0.49	T
GERP RS		1.0
Varity_R		0.61
gMVP		0.032

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: rs10490924; hg19: chr10-124214448;