rs2768551

Positions:

• chr6-108949453-G-A
• chr6-108949453-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ARMC2	NM_032131.6	c.1597-3580G>A		intron_variant		ENST00000392644.9	NP_115507.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC2	ENST00000392644.9	c.1597-3580G>A		intron_variant		1	NM_032131.6	ENSP00000376417	P1
ARMC2	ENST00000368972.7	c.1102-3580G>A		intron_variant		2		ENSP00000357968

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

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.219

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2768551; hg19: chr6-109270656; COSMIC: COSV64553259;