2-231311828-G-A

Variant names:

• chr2-231311828-G-A
• rs7580717
• NM_001352754.2:c.1773+15575G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352754.2(ARMC9):​c.1773+15575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 146,396 control chromosomes in the GnomAD database, including 6,740 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (6740 hom., cov: 28)
• Consequence: ARMC9 NM_001352754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 11 publications found

Genes affected

ARMC9 (HGNC:20730): (armadillo repeat containing 9) Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway. Located in centriole and ciliary basal body. Implicated in Joubert syndrome 30. [provided by Alliance of Genome Resources, Apr 2022]

ARMC9 Gene-Disease associations (from GenCC):

• Joubert syndrome 30

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352754.2. 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
	ARMC9	NM_001352754.2	MANE Select	c.1773+15575G>A		intron	N/A	NP_001339683.2
	ARMC9	NM_001271466.4		c.1773+15575G>A		intron	N/A	NP_001258395.2
	ARMC9	NM_001291656.2		c.1773+15575G>A		intron	N/A	NP_001278585.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC9	ENST00000611582.5	TSL:5 MANE Select	c.1773+15575G>A		intron	N/A	ENSP00000484804.1
	ARMC9	ENST00000349938.8	TSL:1	c.1773+15575G>A		intron	N/A	ENSP00000258417.5
	ARMC9	ENST00000683275.1		c.1908+15575G>A		intron	N/A	ENSP00000506823.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 43342 AN: 146332 Hom.: 6740 Cov.: 28

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.0904

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.296 AC: 43351 AN: 146396 Hom.: 6740 Cov.: 28 AF XY: 0.292 AC XY: 20702 AN XY: 70922

African (AFR) AF: 0.257 AC: 10121 AN: 39458

American (AMR) AF: 0.216 AC: 3114 AN: 14442

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1402 AN: 3438

East Asian (EAS) AF: 0.0912 AC: 454 AN: 4978

South Asian (SAS) AF: 0.169 AC: 767 AN: 4538

European-Finnish (FIN) AF: 0.413 AC: 3811 AN: 9238

Middle Eastern (MID) AF: 0.297 AC: 85 AN: 286

European-Non Finnish (NFE) AF: 0.338 AC: 22675 AN: 67096

Other (OTH) AF: 0.300 AC: 605 AN: 2018

Alfa AF: 0.307 Hom.: 11081

Bravo AF: 0.278

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7580717; hg19: chr2-232176541;