rs2768551

Variant names:

• chr6-108949453-G-A
• rs2768551
• NM_032131.6:c.1597-3580G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-108949453-G-A
• chr6-108949453-G-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.1597-3580G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,190 control chromosomes in the GnomAD database, including 2,732 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 0.18 (2732 hom., cov: 32)
• Consequence: ARMC2 NM_032131.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 10 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=-0.97).
• 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.1597-3580G>A		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.1597-3580G>A		intron_variant	Intron 12 of 17	1	NM_032131.6	ENSP00000376417.4
ARMC2	ENST00000368972.7	c.1102-3580G>A		intron_variant	Intron 11 of 16	2		ENSP00000357968.3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27981 AN: 152072 Hom.: 2732 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.184 AC: 27996 AN: 152190 Hom.: 2732 Cov.: 32 AF XY: 0.185 AC XY: 13758 AN XY: 74422

African (AFR) AF: 0.146 AC: 6049 AN: 41514

American (AMR) AF: 0.247 AC: 3784 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1474 AN: 5180

South Asian (SAS) AF: 0.192 AC: 926 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1572 AN: 10592

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12918 AN: 68004

Other (OTH) AF: 0.219 AC: 464 AN: 2114

Alfa AF: 0.187 Hom.: 347

Bravo AF: 0.194

Asia WGS AF: 0.234 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.063
DANN	Benign	0.31
PhyloP100		-1.8
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: rs2768551; hg19: chr6-109270656; COSMIC: COSV64553259;