6-108963986-A-G

Variant names:

• chr6-108963986-A-G
• rs2273669
• NM_032131.6:c.2153-194A>G

Variant summary

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

The NM_032131.6(ARMC2):​c.2153-194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,116 control chromosomes in the GnomAD database, including 3,314 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 0.19 (3314 hom., cov: 32)
• Consequence: ARMC2 NM_032131.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 66 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC2	NM_032131.6	c.2153-194A>G		intron_variant	Intron 15 of 17	ENST00000392644.9	NP_115507.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC2	ENST00000392644.9	c.2153-194A>G		intron_variant	Intron 15 of 17	1	NM_032131.6	ENSP00000376417.4
ARMC2	ENST00000368972.7	c.1658-194A>G		intron_variant	Intron 14 of 16	2		ENSP00000357968.3
ARMC2	ENST00000481850.1	n.298-194A>G		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28840 AN: 151996 Hom.: 3293 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.190 AC: 28899 AN: 152116 Hom.: 3314 Cov.: 32 AF XY: 0.188 AC XY: 13988 AN XY: 74348

African (AFR) AF: 0.318 AC: 13211 AN: 41494

American (AMR) AF: 0.116 AC: 1772 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 397 AN: 3466

East Asian (EAS) AF: 0.0766 AC: 396 AN: 5168

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4814

European-Finnish (FIN) AF: 0.157 AC: 1661 AN: 10556

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9874 AN: 68002

Other (OTH) AF: 0.185 AC: 392 AN: 2114

Alfa AF: 0.158 Hom.: 9392

Bravo AF: 0.189

Asia WGS AF: 0.144 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.61
PhyloP100		0.0040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2273669; hg19: chr6-109285189;