6-108858233-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032131.6(ARMC2):c.253A>G(p.Arg85Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARMC2 NM_032131.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.18

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC2	NM_032131.6	c.253A>G	p.Arg85Gly	missense_variant	3/18	ENST00000392644.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC2	ENST00000392644.9	c.253A>G	p.Arg85Gly	missense_variant	3/18	1	NM_032131.6	P1
ARMC2	ENST00000237512.4	c.253A>G	p.Arg85Gly	missense_variant	3/5	2
ARMC2	ENST00000368972.7	c.-205+3748A>G		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458908 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725768

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.253A>G (p.R85G) alteration is located in exon 3 (coding exon 2) of the ARMC2 gene. This alteration results from a A to G substitution at nucleotide position 253, causing the arginine (R) at amino acid position 85 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.37	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	-0.083	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	0.92	D;D
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.93	P;.
Vest4		0.52
MutPred		0.24		Loss of stability (P = 0.0582);Loss of stability (P = 0.0582);
MVP		0.94
MPC		0.45
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.39
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-109179436;