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GeneBe

6-108868829-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_032131.6(ARMC2):c.297G>A(p.Pro99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000844 in 1,608,220 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 3 hom. )

Consequence

ARMC2
NM_032131.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.59
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-108868829-G-A is Benign according to our data. Variant chr6-108868829-G-A is described in ClinVar as [Benign]. Clinvar id is 3033187.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.6 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00505 (768/152192) while in subpopulation AFR AF= 0.0176 (729/41526). AF 95% confidence interval is 0.0165. There are 4 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARMC2NM_032131.6 linkuse as main transcriptc.297G>A p.Pro99= synonymous_variant 4/18 ENST00000392644.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARMC2ENST00000392644.9 linkuse as main transcriptc.297G>A p.Pro99= synonymous_variant 4/181 NM_032131.6 P1Q8NEN0-1
ARMC2ENST00000237512.4 linkuse as main transcriptc.297G>A p.Pro99= synonymous_variant 4/52
ARMC2ENST00000368972.7 linkuse as main transcriptc.-199G>A 5_prime_UTR_variant 3/172 Q8NEN0-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00505
AC:
768
AN:
152074
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0176
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00183
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:
0.0000441
Gnomad OTH
AF:
0.00384
GnomAD3 exomes
AF:
0.00127
AC:
310
AN:
244698
Hom.:
1
AF XY:
0.000944
AC XY:
125
AN XY:
132464
show subpopulations
Gnomad AFR exome
AF:
0.0166
Gnomad AMR exome
AF:
0.000955
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000135
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000898
Gnomad OTH exome
AF:
0.000843
GnomAD4 exome
AF:
0.000405
AC:
590
AN:
1456028
Hom.:
3
Cov.:
31
AF XY:
0.000348
AC XY:
252
AN XY:
724422
show subpopulations
Gnomad4 AFR exome
AF:
0.0146
Gnomad4 AMR exome
AF:
0.00103
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000820
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.000666
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00505
AC:
768
AN:
152192
Hom.:
4
Cov.:
32
AF XY:
0.00489
AC XY:
364
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0176
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00380
Alfa
AF:
0.00131
Hom.:
0
Bravo
AF:
0.00540
Asia WGS
AF:
0.00173
AC:
7
AN:
3478

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 submitterclinical testingPreventionGenetics, part of Exact SciencesJan 20, 2020This 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
BayesDel_noAF
Benign
-0.76
Cadd
Benign
4.8
Dann
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
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.

Other links and lift over

dbSNP: rs73524086; hg19: chr6-109190032; API