1-225937465-G-A
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_003240.5(LEFTY2):c.1077C>T(p.Leu359=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
LEFTY2
NM_003240.5 synonymous
NM_003240.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.90
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 1-225937465-G-A is Benign according to our data. Variant chr1-225937465-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 695459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.9 with no splicing effect.
BS2
?
High AC in GnomAd at 33 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEFTY2 | NM_003240.5 | c.1077C>T | p.Leu359= | synonymous_variant | 4/4 | ENST00000366820.10 | |
LEFTY2 | NM_001172425.3 | c.975C>T | p.Leu325= | synonymous_variant | 5/5 | ||
LEFTY2 | XM_011544266.2 | c.*450C>T | 3_prime_UTR_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEFTY2 | ENST00000366820.10 | c.1077C>T | p.Leu359= | synonymous_variant | 4/4 | 1 | NM_003240.5 | P1 | |
ENST00000513672.1 | n.93C>T | non_coding_transcript_exon_variant | 1/2 | 2 | |||||
LEFTY2 | ENST00000420304.6 | c.975C>T | p.Leu325= | synonymous_variant | 5/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
33
AN:
152178
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000458 AC: 115AN: 250894Hom.: 0 AF XY: 0.000464 AC XY: 63AN XY: 135772
GnomAD3 exomes
AF:
AC:
115
AN:
250894
Hom.:
AF XY:
AC XY:
63
AN XY:
135772
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000255 AC: 372AN: 1461640Hom.: 0 Cov.: 29 AF XY: 0.000281 AC XY: 204AN XY: 727120
GnomAD4 exome
AF:
AC:
372
AN:
1461640
Hom.:
Cov.:
29
AF XY:
AC XY:
204
AN XY:
727120
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74346
GnomAD4 genome
?
AF:
AC:
33
AN:
152178
Hom.:
Cov.:
32
AF XY:
AC XY:
18
AN XY:
74346
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Left-right axis malformations Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at