rs773383669

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001029861.3(NANOS2):​c.155C>T​(p.Ala52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,740 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A52E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NANOS2
NM_001029861.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0370
Variant links:
Genes affected
NANOS2 (HGNC:23292): (nanos C2HC-type zinc finger 2) Predicted to enable mRNA binding activity. Involved in negative regulation of translation and positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay. Located in nucleus and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.044896156).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NANOS2NM_001029861.3 linkc.155C>T p.Ala52Val missense_variant Exon 1 of 1 ENST00000341294.4 NP_001025032.1 P60321

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NANOS2ENST00000341294.4 linkc.155C>T p.Ala52Val missense_variant Exon 1 of 1 6 NM_001029861.3 ENSP00000341021.2 P60321

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000479
AC:
12
AN:
250432
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135584
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
0.0000116
AC:
17
AN:
1461740
Hom.:
0
Cov.:
32
AF XY:
0.00000825
AC XY:
6
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000189
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.155C>T (p.A52V) alteration is located in exon 1 (coding exon 1) of the NANOS2 gene. This alteration results from a C to T substitution at nucleotide position 155, causing the alanine (A) at amino acid position 52 to be replaced by a valine (V). 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
0.063
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.92
DANN
Benign
0.95
DEOGEN2
Benign
0.18
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.045
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.012
Sift
Benign
0.32
T
Sift4G
Benign
0.33
T
Polyphen
0.063
B
Vest4
0.062
MutPred
0.18
Loss of relative solvent accessibility (P = 0.1807);
MVP
0.082
MPC
0.50
ClinPred
0.018
T
GERP RS
-0.18
Varity_R
0.030
gMVP
0.43

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: rs773383669; hg19: chr19-46417797; COSMIC: COSV58025340; API