Variant 6-108854422-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_032131.6(ARMC2):c.155A>C(p.Gln52Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00199 in 1,613,620 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 9 hom. )

Consequence

ARMC2
NM_032131.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.58

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00954929).

BP6

Variant 6-108854422-A-C is Benign according to our data. Variant chr6-108854422-A-C is described in ClinVar as [Benign]. Clinvar id is 3050582.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC2	NM_032131.6 linkuse as main transcript	c.155A>C	p.Gln52Pro	missense_variant	2/18	ENST00000392644.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC2	ENST00000392644.9 linkuse as main transcript	c.155A>C	p.Gln52Pro	missense_variant	2/18	1	NM_032131.6	P1	Q8NEN0-1
ARMC2	ENST00000237512.4 linkuse as main transcript	c.155A>C	p.Gln52Pro	missense_variant	2/5	2
ARMC2	ENST00000368972.7 linkuse as main transcript	c.-268A>C		5_prime_UTR_variant	2/17	2			Q8NEN0-2

Frequencies

GnomAD3 genomes

AF:

0.00155

AC:

235

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00197

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00196

AC:

492

AN:

251036

Hom.:

AF XY:

0.00211

AC XY:

286

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00208

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00204

AC:

2976

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

1470

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00198

Gnomad4 OTH exome

AF:

0.00260

GnomAD4 genome

AF:

0.00155

AC:

235

AN:

151968

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00197

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00247

Hom.:

Bravo

AF:

0.00147

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00185

AC:

225

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ARMC2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.070

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.068

T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.0095

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.4

N;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.024

D;D

Polyphen

1.0

D;.

Vest4

0.84

MVP

0.78

MPC

0.63

ClinPred

0.043

GERP RS

5.3

Varity_R

0.45

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over