rs2798641

Variant names:

• chr6-108946847-C-T
• rs2798641
• NM_032131.6:c.1597-6186C>T

Variant summary

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

The NM_032131.6(ARMC2):​c.1597-6186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,106 control chromosomes in the GnomAD database, including 2,252 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 0.16 (2252 hom., cov: 32)
• Consequence: ARMC2 NM_032131.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517
• Publications: 33 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC2	NM_032131.6	c.1597-6186C>T		intron_variant	Intron 12 of 17	ENST00000392644.9	NP_115507.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC2	ENST00000392644.9	c.1597-6186C>T		intron_variant	Intron 12 of 17	1	NM_032131.6	ENSP00000376417.4
ARMC2	ENST00000368972.7	c.1102-6186C>T		intron_variant	Intron 11 of 16	2		ENSP00000357968.3

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23565 AN: 151988 Hom.: 2251 Cov.: 32

Gnomad AFR AF: 0.0536

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.155 AC: 23577 AN: 152106 Hom.: 2252 Cov.: 32 AF XY: 0.157 AC XY: 11651 AN XY: 74352

African (AFR) AF: 0.0535 AC: 2222 AN: 41502

American (AMR) AF: 0.234 AC: 3571 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1472 AN: 5178

South Asian (SAS) AF: 0.189 AC: 908 AN: 4814

European-Finnish (FIN) AF: 0.146 AC: 1541 AN: 10560

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12644 AN: 67984

Other (OTH) AF: 0.196 AC: 413 AN: 2112

Alfa AF: 0.181 Hom.: 9983

Bravo AF: 0.160

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		0.52
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: rs2798641; hg19: chr6-109268050;