X-9873708-C-T
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6BP7BS2_Supporting
The NM_001649.4(SHROOM2):c.222C>T(p.Ile74Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,209,780 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000015 ( 0 hom. 8 hem. )
Consequence
SHROOM2
NM_001649.4 synonymous
NM_001649.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.596
Genes affected
SHROOM2 (HGNC:630): (shroom family member 2) This gene represents the human homolog of Xenopus laevis apical protein (APX) gene, which is implicated in amiloride-sensitive sodium channel activity. It is expressed in endothelial cells and facilitates the formation of a contractile network within endothelial cells. Depletion of this gene results in an increase in endothelial sprouting, migration, and angiogenesis. This gene is highly expressed in the retina, and is a strong candidate for ocular albinism type 1 syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant X-9873708-C-T is Benign according to our data. Variant chrX-9873708-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3060870.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.596 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 8 geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000357 AC: 4AN: 111958Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1AN XY: 34150
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GnomAD3 exomes AF: 0.0000600 AC: 11AN: 183381Hom.: 0 AF XY: 0.0000737 AC XY: 5AN XY: 67823
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GnomAD4 exome AF: 0.0000155 AC: 17AN: 1097768Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 8AN XY: 363126
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GnomAD4 genome AF: 0.0000357 AC: 4AN: 112012Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34214
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
SHROOM2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 15, 2019 | This 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at