Variant chr6-108876185-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 ENST00000392644.9(ARMC2):c.506A>G(p.Asp169Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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
ENST00000392644.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

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:

ARMC2 (HGNC:):

ARMC2 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=0.13380536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC2	NM_032131.6 linkuse as main transcript	c.506A>G	p.Asp169Gly	missense_variant	5/18	ENST00000392644.9	NP_115507.4	Q8NEN0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARMC2	ENST00000392644.9 linkuse as main transcript	c.506A>G	p.Asp169Gly	missense_variant	5/18	1	NM_032131.6	ENSP00000376417.4	Q8NEN0-1
ARMC2	ENST00000368972.7 linkuse as main transcript	c.11A>G	p.Asp4Gly	missense_variant	4/17	2		ENSP00000357968.3	Q8NEN0-2
ARMC2	ENST00000237512.4 linkuse as main transcript	c.506A>G	p.Asp169Gly	missense_variant	5/5	2		ENSP00000237512.4	A0A0A0MQT2
ARMC2	ENST00000414610.1 linkuse as main transcript	c.59A>G	p.Asp20Gly	missense_variant	2/3	5		ENSP00000393191.1	H0Y4P5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726340

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.:

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

Apr 18, 2024

The c.506A>G (p.D169G) 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 506, causing the aspartic acid (D) at amino acid position 169 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

0.086

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.053

.;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.034

D;T;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.22

.;B;.

Vest4

0.25

MutPred

0.30

.;Loss of ubiquitination at K173 (P = 0.0561);Loss of ubiquitination at K173 (P = 0.0561);

MVP

0.68

MPC

0.18

ClinPred

0.13

GERP RS

3.6

Varity_R

0.052

gMVP

0.25

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over