6-108897055-A-G

Variant names:

• chr6-108897055-A-G
• rs11153135
• NM_032131.6:c.748+2512A>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.748+2512A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,262 control chromosomes in the GnomAD database, including 1,239 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 0.11 (1239 hom., cov: 32)
• Consequence: ARMC2 NM_032131.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032131.6. 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
	ARMC2	NM_032131.6	MANE Select	c.748+2512A>G		intron	N/A	NP_115507.4
	ARMC2	NM_001286609.2		c.253+2512A>G		intron	N/A	NP_001273538.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC2	ENST00000392644.9	TSL:1 MANE Select	c.748+2512A>G		intron	N/A	ENSP00000376417.4
	ARMC2	ENST00000368972.7	TSL:2	c.253+2512A>G		intron	N/A	ENSP00000357968.3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17013 AN: 152144 Hom.: 1241 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.112 AC: 17001 AN: 152262 Hom.: 1239 Cov.: 32 AF XY: 0.114 AC XY: 8488 AN XY: 74448

African (AFR) AF: 0.0275 AC: 1143 AN: 41564

American (AMR) AF: 0.0890 AC: 1361 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3472

East Asian (EAS) AF: 0.0601 AC: 312 AN: 5194

South Asian (SAS) AF: 0.174 AC: 841 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1898 AN: 10596

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10525 AN: 67998

Other (OTH) AF: 0.108 AC: 229 AN: 2112

Alfa AF: 0.122 Hom.: 162

Bravo AF: 0.0985

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		0.15
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: rs11153135; hg19: chr6-109218258;