GeneBe

NM_003240.5:c.69C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_003240.5(LEFTY2):​c.69C>A​(p.Thr23Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T23T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LEFTY2
NM_003240.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Publications

0 publications found
Variant links:
Genes affected
LEFTY2 (HGNC:3122): (left-right determination factor 2) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in left-right asymmetry determination of organ systems during development. The protein may also play a role in endometrial bleeding. Mutations in this gene have been associated with left-right axis malformations, particularly in the heart and lungs. Some types of infertility have been associated with dysregulated expression of this gene in the endometrium. This gene is closely linked to both a related family member and a related pseudogene. This gene encodes multiple isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]
LEFTY2 Gene-Disease associations (from GenCC):
  • visceral heterotaxy
    Inheritance: AD Classification: LIMITED Submitted by: G2P
  • congenital heart disease
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP7
Synonymous conserved (PhyloP=-1.71 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LEFTY2NM_003240.5 linkc.69C>A p.Thr23Thr synonymous_variant Exon 1 of 4 ENST00000366820.10 NP_003231.2 O00292-1A1NY82
LEFTY2NM_001172425.3 linkc.69C>A p.Thr23Thr synonymous_variant Exon 1 of 5 NP_001165896.1 O00292-2
LEFTY2XM_011544266.2 linkc.69C>A p.Thr23Thr synonymous_variant Exon 1 of 4 XP_011542568.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LEFTY2ENST00000366820.10 linkc.69C>A p.Thr23Thr synonymous_variant Exon 1 of 4 1 NM_003240.5 ENSP00000355785.5 O00292-1
LEFTY2ENST00000420304.6 linkc.69C>A p.Thr23Thr synonymous_variant Exon 1 of 5 2 ENSP00000388009.2 O00292-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1452498
Hom.:
0
Cov.:
32
AF XY:
0.00000139
AC XY:
1
AN XY:
721734
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33292
American (AMR)
AF:
0.00
AC:
0
AN:
44056
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25936
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39474
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85666
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51254
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5092
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1107896
Other (OTH)
AF:
0.00
AC:
0
AN:
59832
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.039
DANN
Benign
0.65
PhyloP100
-1.7
PromoterAI
-0.0016
Neutral
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs750632817; hg19: chr1-226128772; API