chr1-225936870-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_003240.5(LEFTY2):c.*571C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000659 in 156,304 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 Benign (★).
Frequency
Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 0 hom. )
Consequence
LEFTY2
NM_003240.5 3_prime_UTR
NM_003240.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.715
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
?
Variant 1-225936870-G-A is Benign according to our data. Variant chr1-225936870-G-A is described in ClinVar as [Benign]. Clinvar id is 876161.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000644 (98/152228) while in subpopulation SAS AF= 0.0191 (92/4816). AF 95% confidence interval is 0.0159. There are 0 homozygotes in gnomad4. There are 81 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 99 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEFTY2 | NM_003240.5 | c.*571C>T | 3_prime_UTR_variant | 4/4 | ENST00000366820.10 | ||
LEFTY2 | NM_001172425.3 | c.*571C>T | 3_prime_UTR_variant | 5/5 | |||
LEFTY2 | XM_011544266.2 | c.*1045C>T | 3_prime_UTR_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEFTY2 | ENST00000366820.10 | c.*571C>T | 3_prime_UTR_variant | 4/4 | 1 | NM_003240.5 | P1 | ||
ENST00000513672.1 | n.176-293C>T | intron_variant, non_coding_transcript_variant | 2 | ||||||
LEFTY2 | ENST00000420304.6 | c.*571C>T | 3_prime_UTR_variant | 5/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000651 AC: 99AN: 152110Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00123 AC: 5AN: 4076Hom.: 0 Cov.: 0 AF XY: 0.00146 AC XY: 3AN XY: 2052
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Left-right axis malformations Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at