Variant 6-108876335-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032131.6(ARMC2):c.656A>G(p.His219Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

ARMC2
NM_032131.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.389

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:

LOC124901373 (HGNC:):

LOC124901373 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13665602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC2	NM_032131.6 linkuse as main transcript	c.656A>G	p.His219Arg	missense_variant	5/18	ENST00000392644.9
LOC124901373	XM_047419631.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC2	ENST00000392644.9 linkuse as main transcript	c.656A>G	p.His219Arg	missense_variant	5/18	1	NM_032131.6	P1	Q8NEN0-1
ARMC2	ENST00000368972.7 linkuse as main transcript	c.161A>G	p.His54Arg	missense_variant	4/17	2			Q8NEN0-2
ARMC2	ENST00000237512.4 linkuse as main transcript	c.656A>G	p.His219Arg	missense_variant	5/5	2
ARMC2	ENST00000414610.1 linkuse as main transcript	c.212A>G	p.His71Arg	missense_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.656A>G (p.H219R) alteration is located in exon 5 (coding exon 4) of the ARMC2 gene. This alteration results from a A to G substitution at nucleotide position 656, causing the histidine (H) at amino acid position 219 to be replaced by an arginine (R). 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

0.066

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

Cadd

Benign

0.37

Dann

Benign

0.83

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.81

N;N;N

REVEL

Benign

0.043

Sift

Benign

0.084

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.11

.;B;.

Vest4

0.038

MutPred

0.21

.;Gain of MoRF binding (P = 0.0126);Gain of MoRF binding (P = 0.0126);

MVP

0.55

MPC

0.16

ClinPred

0.076

GERP RS

-0.16

Varity_R

0.039

gMVP

0.25

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