rs12209480

Variant names:

• chr6-108958008-G-A
• rs12209480
• NM_032131.6:c.1916-3564G>A

Variant summary

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

The NM_032131.6(ARMC2):​c.1916-3564G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 152,190 control chromosomes in the GnomAD database, including 678 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 0.088 (678 hom., cov: 32)
• Consequence: ARMC2 NM_032131.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 6 publications found

Genes affected

ARMC2 (HGNC:23045): (armadillo repeat containing 2) Involved in sperm axoneme assembly. Implicated in spermatogenic failure 38. [provided by Alliance of Genome Resources, Apr 2022]

ARMC2 Gene-Disease associations (from GenCC):

• spermatogenic failure 38

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC2	NM_032131.6	c.1916-3564G>A		intron_variant	Intron 13 of 17	ENST00000392644.9	NP_115507.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC2	ENST00000392644.9	c.1916-3564G>A		intron_variant	Intron 13 of 17	1	NM_032131.6	ENSP00000376417.4
ARMC2	ENST00000368972.7	c.1421-3564G>A		intron_variant	Intron 12 of 16	2		ENSP00000357968.3

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13379 AN: 152072 Hom.: 677 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.0414

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0880 AC: 13390 AN: 152190 Hom.: 678 Cov.: 32 AF XY: 0.0904 AC XY: 6729 AN XY: 74412

African (AFR) AF: 0.0851 AC: 3533 AN: 41524

American (AMR) AF: 0.0535 AC: 818 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3468

East Asian (EAS) AF: 0.0417 AC: 216 AN: 5176

South Asian (SAS) AF: 0.181 AC: 870 AN: 4814

European-Finnish (FIN) AF: 0.139 AC: 1471 AN: 10584

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5980 AN: 68016

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0843 Hom.: 1105

Bravo AF: 0.0763

Asia WGS AF: 0.0910 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.44
PhyloP100		0.20
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: rs12209480; hg19: chr6-109279211;