X-9873674-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS2_Supporting
The NM_001649.4(SHROOM2):c.188C>T(p.Ala63Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 1,210,001 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000014 ( 0 hom. 2 hem. )
Consequence
SHROOM2
NM_001649.4 missense
NM_001649.4 missense
Scores
3
8
6
Clinical Significance
Conservation
PhyloP100: 4.42
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 Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.815
BS2
High Hemizygotes in GnomAdExome4 at 2 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: 0.00000891 AC: 1AN: 112187Hom.: 0 Cov.: 23 AF XY: 0.0000291 AC XY: 1AN XY: 34361
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GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183110Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67562
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GnomAD4 exome AF: 0.0000137 AC: 15AN: 1097759Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 2AN XY: 363129
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GnomAD4 genome AF: 0.00000891 AC: 1AN: 112242Hom.: 0 Cov.: 23 AF XY: 0.0000290 AC XY: 1AN XY: 34426
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.188C>T (p.A63V) alteration is located in exon 2 (coding exon 2) of the SHROOM2 gene. This alteration results from a C to T substitution at nucleotide position 188, causing the alanine (A) at amino acid position 63 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Pathogenic
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at