chr1-225939905-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000366820.10(LEFTY2):ā€‹c.348C>Gā€‹(p.Ala116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000637 in 1,413,808 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 (ā˜…). Synonymous variant affecting the same amino acid position (i.e. A116A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000064 ( 0 hom. )

Consequence

LEFTY2
ENST00000366820.10 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.69
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 1-225939905-G-C is Benign according to our data. Variant chr1-225939905-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2882097.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.69 with no splicing effect.
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LEFTY2NM_003240.5 linkuse as main transcriptc.348C>G p.Ala116= synonymous_variant 2/4 ENST00000366820.10 NP_003231.2
LEFTY2XM_011544266.2 linkuse as main transcriptc.348C>G p.Ala116= synonymous_variant 2/4 XP_011542568.1
LEFTY2NM_001172425.3 linkuse as main transcriptc.280-34C>G intron_variant NP_001165896.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LEFTY2ENST00000366820.10 linkuse as main transcriptc.348C>G p.Ala116= synonymous_variant 2/41 NM_003240.5 ENSP00000355785 P1O00292-1
LEFTY2ENST00000420304.6 linkuse as main transcriptc.280-34C>G intron_variant 2 ENSP00000388009 O00292-2
LEFTY2ENST00000474493.1 linkuse as main transcriptn.197C>G non_coding_transcript_exon_variant 1/23

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000127
AC:
2
AN:
157386
Hom.:
0
AF XY:
0.0000115
AC XY:
1
AN XY:
86794
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000153
Gnomad OTH exome
AF:
0.000225
GnomAD4 exome
AF:
0.00000637
AC:
9
AN:
1413808
Hom.:
0
Cov.:
34
AF XY:
0.00000714
AC XY:
5
AN XY:
700690
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.0000256
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:
0.00000274
Gnomad4 OTH exome
AF:
0.0000509
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 30, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.46
DANN
Benign
0.77

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755946624; hg19: chr1-226127605; API