chr14-67620953-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001172.4(ARG2):ā€‹c.171G>Cā€‹(p.Arg57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

ARG2
NM_001172.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.445
Variant links:
Genes affected
ARG2 (HGNC:664): (arginase 2) Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exists (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type II isoform encoded by this gene, is located in the mitochondria and expressed in extra-hepatic tissues, especially kidney. The physiologic role of this isoform is poorly understood; it is thought to play a role in nitric oxide and polyamine metabolism. Transcript variants of the type II gene resulting from the use of alternative polyadenylation sites have been described. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARG2NM_001172.4 linkuse as main transcriptc.171G>C p.Arg57Ser missense_variant 2/8 ENST00000261783.4
GPHNXM_047430879.1 linkuse as main transcriptc.1313-114242G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARG2ENST00000261783.4 linkuse as main transcriptc.171G>C p.Arg57Ser missense_variant 2/81 NM_001172.4 P1
ARG2ENST00000556491.1 linkuse as main transcriptn.169G>C non_coding_transcript_exon_variant 2/45
ARG2ENST00000557120.5 linkuse as main transcriptn.213G>C non_coding_transcript_exon_variant 2/52

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251492
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461802
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsJan 03, 2024The c.171G>C (p.R57S) alteration is located in exon 2 (coding exon 2) of the ARG2 gene. This alteration results from a G to C substitution at nucleotide position 171, causing the arginine (R) at amino acid position 57 to be replaced by a serine (S). 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
Uncertain
0.50
BayesDel_addAF
Benign
-0.095
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.64
D
Eigen
Benign
-0.0030
Eigen_PC
Benign
-0.061
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.89
D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.75
D
MetaSVM
Benign
-0.34
T
MutationAssessor
Benign
1.8
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.50
Sift
Benign
0.15
T
Sift4G
Benign
0.25
T
Polyphen
0.82
P
Vest4
0.81
MutPred
0.56
Gain of catalytic residue at S60 (P = 0);
MVP
0.49
MPC
0.42
ClinPred
0.60
D
GERP RS
-0.79
Varity_R
0.84
gMVP
0.80

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.

Other links and lift over

dbSNP: rs763512011; hg19: chr14-68087670; API