chr1-225936945-A-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_003240.5(LEFTY2):c.*496T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 168,312 control chromosomes in the GnomAD database, including 370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.038 ( 369 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 1 hom. )
Consequence
LEFTY2
NM_003240.5 3_prime_UTR
NM_003240.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0950
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=-0.88).
BP6
Variant 1-225936945-A-C is Benign according to our data. Variant chr1-225936945-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 295962.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEFTY2 | NM_003240.5 | c.*496T>G | 3_prime_UTR_variant | 4/4 | ENST00000366820.10 | ||
LEFTY2 | NM_001172425.3 | c.*496T>G | 3_prime_UTR_variant | 5/5 | |||
LEFTY2 | XM_011544266.2 | c.*970T>G | 3_prime_UTR_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEFTY2 | ENST00000366820.10 | c.*496T>G | 3_prime_UTR_variant | 4/4 | 1 | NM_003240.5 | P1 | ||
ENST00000513672.1 | n.176-368T>G | intron_variant, non_coding_transcript_variant | 2 | ||||||
LEFTY2 | ENST00000420304.6 | c.*496T>G | 3_prime_UTR_variant | 5/5 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0378 AC: 5754AN: 152130Hom.: 367 Cov.: 32
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GnomAD4 exome AF: 0.00224 AC: 36AN: 16064Hom.: 1 Cov.: 0 AF XY: 0.00184 AC XY: 16AN XY: 8694
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GnomAD4 genome AF: 0.0379 AC: 5765AN: 152248Hom.: 369 Cov.: 32 AF XY: 0.0362 AC XY: 2696AN XY: 74448
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Left-right axis malformations Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
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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