chr2-219055843-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002181.4(IHH):c.600G>A(p.Thr200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 1,609,750 control chromosomes in the GnomAD database, including 8,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.10 ( 803 hom., cov: 32)
Exomes 𝑓: 0.099 ( 7261 hom. )
Consequence
IHH
NM_002181.4 synonymous
NM_002181.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.65
Genes affected
IHH (HGNC:5956): (Indian hedgehog signaling molecule) This gene encodes a member of the hedgehog family of proteins. The encoded preproprotein is proteolytically processed to generate multiple protein products, including an N-terminal fragment that is involved in signaling. Hedgehog family proteins are essential secreted signaling molecules that regulate a variety of developmental processes including growth, patterning and morphogenesis. The protein encoded by this gene specifically plays a role in bone growth and differentiation. Mutations in this gene are the cause of brachydactyly type A1, which is characterized by shortening or malformation of the fingers and toes. Mutations in this gene are also the cause of acrocapitofemoral dysplasia. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 2-219055843-C-T is Benign according to our data. Variant chr2-219055843-C-T is described in ClinVar as [Benign]. Clinvar id is 334443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219055843-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-4.65 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IHH | NM_002181.4 | c.600G>A | p.Thr200= | synonymous_variant | 3/3 | ENST00000295731.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IHH | ENST00000295731.7 | c.600G>A | p.Thr200= | synonymous_variant | 3/3 | 1 | NM_002181.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.103 AC: 15594AN: 152134Hom.: 799 Cov.: 32
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GnomAD3 exomes AF: 0.100 AC: 24420AN: 243016Hom.: 1251 AF XY: 0.0987 AC XY: 13097AN XY: 132710
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GnomAD4 exome AF: 0.0986 AC: 143680AN: 1457498Hom.: 7261 Cov.: 36 AF XY: 0.0984 AC XY: 71369AN XY: 725192
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GnomAD4 genome AF: 0.103 AC: 15619AN: 152252Hom.: 803 Cov.: 32 AF XY: 0.101 AC XY: 7548AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 19, 2018 | This variant is associated with the following publications: (PMID: 14651602) - |
Acrocapitofemoral dysplasia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Brachydactyly type A1 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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at