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GeneBe

9-124014131-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_004789.4(LHX2):c.291C>T(p.Asp97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,613,466 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0038 ( 11 hom. )

Consequence

LHX2
NM_004789.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0410
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 -9 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=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-124014131-C-T is Benign according to our data. Variant chr9-124014131-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3056509.Status of the report is criteria_provided_single_submitter, 1 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=0.041 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 413 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LHX2NM_004789.4 linkuse as main transcriptc.291C>T p.Asp97= synonymous_variant 2/5 ENST00000373615.9
LHX2XM_006717323.4 linkuse as main transcriptc.291C>T p.Asp97= synonymous_variant 2/6
LHX2XM_047424082.1 linkuse as main transcriptc.291C>T p.Asp97= synonymous_variant 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LHX2ENST00000373615.9 linkuse as main transcriptc.291C>T p.Asp97= synonymous_variant 2/51 NM_004789.4 P1
LHX2ENST00000446480.5 linkuse as main transcriptc.285C>T p.Asp95= synonymous_variant 2/52
LHX2ENST00000560961.2 linkuse as main transcriptc.168C>T p.Asp56= synonymous_variant 2/33

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00271
AC:
413
AN:
152184
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000700
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00707
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00132
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00362
Gnomad OTH
AF:
0.00622
GnomAD3 exomes
AF:
0.00252
AC:
630
AN:
250462
Hom.:
1
AF XY:
0.00239
AC XY:
324
AN XY:
135774
show subpopulations
Gnomad AFR exome
AF:
0.000865
Gnomad AMR exome
AF:
0.00301
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00102
Gnomad NFE exome
AF:
0.00407
Gnomad OTH exome
AF:
0.00376
GnomAD4 exome
AF:
0.00381
AC:
5565
AN:
1461164
Hom.:
11
Cov.:
33
AF XY:
0.00362
AC XY:
2635
AN XY:
726902
show subpopulations
Gnomad4 AFR exome
AF:
0.000747
Gnomad4 AMR exome
AF:
0.00324
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000313
Gnomad4 FIN exome
AF:
0.00114
Gnomad4 NFE exome
AF:
0.00458
Gnomad4 OTH exome
AF:
0.00358
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00271
AC:
413
AN:
152302
Hom.:
1
Cov.:
33
AF XY:
0.00274
AC XY:
204
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000697
Gnomad4 AMR
AF:
0.00706
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00132
Gnomad4 NFE
AF:
0.00362
Gnomad4 OTH
AF:
0.00616
Alfa
AF:
0.00340
Hom.:
0
Bravo
AF:
0.00292
EpiCase
AF:
0.00431
EpiControl
AF:
0.00433

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

LHX2-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesAug 15, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
2.2
Dann
Benign
0.83

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: rs144291200; hg19: chr9-126776410; API