19-45914542-C-T

Variant names:

• chr19-45914542-C-T
• rs911158197
• NM_001029861.3:c.152G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001029861.3(NANOS2):​c.152G>A​(p.Gly51Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000021 (0 hom.)
• Consequence: NANOS2 NM_001029861.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.463

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]

ACMG classification

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=0.06160009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NANOS2	NM_001029861.3	c.152G>A	p.Gly51Glu	missense_variant	Exon 1 of 1	ENST00000341294.4	NP_001025032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NANOS2	ENST00000341294.4	c.152G>A	p.Gly51Glu	missense_variant	Exon 1 of 1	6	NM_001029861.3	ENSP00000341021.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461800 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 727214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.0000261

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.152G>A (p.G51E) alteration is located in exon 1 (coding exon 1) of the NANOS2 gene. This alteration results from a G to A substitution at nucleotide position 152, causing the glycine (G) at amino acid position 51 to be replaced by a glutamic acid (E). 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	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.50
DANN	Benign	0.36
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.016
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.11
MutPred		0.20		Gain of solvent accessibility (P = 0.0789);
MVP		0.043
MPC		0.66
ClinPred		0.055	T
GERP RS		-2.8
Varity_R		0.026
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

Other links and lift over

dbSNP: rs911158197; hg19: chr19-46417800;