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GeneBe

rs61734362

chr9-124021136-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004789.4(LHX2):c.765C>T(p.Asp255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,614,130 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0026 ( 133 hom. )

Consequence

LHX2
NM_004789.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.878
Variant links:
Genes affected
LHX2 (HGNC:6594): (LIM homeobox 2) This gene encodes a protein belonging to a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein may function as a transcriptional regulator. The protein can recapitulate or rescue phenotypes in Drosophila caused by a related protein, suggesting conservation of function during evolution. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-124021136-C-T is Benign according to our data. Variant chr9-124021136-C-T is described in ClinVar as [Benign]. Clinvar id is 770200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.878 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LHX2NM_004789.4 linkuse as main transcriptc.765C>T p.Asp255= synonymous_variant 4/5 ENST00000373615.9
LHX2XM_006717323.4 linkuse as main transcriptc.765C>T p.Asp255= synonymous_variant 4/6
LHX2XM_047424082.1 linkuse as main transcriptc.765C>T p.Asp255= synonymous_variant 4/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LHX2ENST00000373615.9 linkuse as main transcriptc.765C>T p.Asp255= synonymous_variant 4/51 NM_004789.4 P1
LHX2ENST00000446480.5 linkuse as main transcriptc.783C>T p.Asp261= synonymous_variant 4/52
LHX2ENST00000488674.2 linkuse as main transcriptc.168C>T p.Asp56= synonymous_variant 2/43

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00354
AC:
539
AN:
152222
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0273
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0123
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.0107
AC:
2676
AN:
251048
Hom.:
98
AF XY:
0.00797
AC XY:
1082
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.000924
Gnomad AMR exome
AF:
0.0701
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00941
Gnomad SAS exome
AF:
0.000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.00701
GnomAD4 exome
AF:
0.00262
AC:
3823
AN:
1461790
Hom.:
133
Cov.:
30
AF XY:
0.00228
AC XY:
1661
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.0646
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0174
Gnomad4 SAS exome
AF:
0.000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000405
Gnomad4 OTH exome
AF:
0.00180
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00354
AC:
539
AN:
152340
Hom.:
9
Cov.:
32
AF XY:
0.00366
AC XY:
273
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.000962
Gnomad4 AMR
AF:
0.0273
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0123
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00120
Hom.:
3
Bravo
AF:
0.00657
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

LHX2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesSep 25, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 27, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
8.5
Dann
Benign
0.93

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: rs61734362; hg19: chr9-126783415; API