Variant 6-108899778-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032131.6(ARMC2):c.833G>A(p.Arg278His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,611,858 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

ARMC2
NM_032131.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016225457).

BP6

Variant 6-108899778-G-A is Benign according to our data. Variant chr6-108899778-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2370864.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.833G>A	p.Arg278His	missense_variant	7/18	ENST00000392644.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC2	ENST00000392644.9 linkuse as main transcript	c.833G>A	p.Arg278His	missense_variant	7/18	1	NM_032131.6	P1	Q8NEN0-1
ARMC2	ENST00000368972.7 linkuse as main transcript	c.338G>A	p.Arg113His	missense_variant	6/17	2			Q8NEN0-2

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151816

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000381

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

249138

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

134630

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000665

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000147

AC:

215

AN:

1460042

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

726260

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000698

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000158

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000158

AC:

AN:

151816

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000381

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.73

Cadd

Benign

3.2

Dann

Benign

0.31

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.49

N;N

REVEL

Benign

0.041

Sift

Benign

1.0

T;T

Sift4G

Benign

0.92

T;T

Polyphen

0.0

.;B

Vest4

0.045

MVP

0.37

MPC

0.16

ClinPred

0.0095

GERP RS

-2.4

Varity_R

0.035

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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