rs2232562
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000423.3(KRT2):c.1650C>T(p.Gly550=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,613,806 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 127 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 129 hom. )
Consequence
KRT2
NM_000423.3 synonymous
NM_000423.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.02
Genes affected
KRT2 (HGNC:6439): (keratin 2) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is expressed largely in the upper spinous layer of epidermal keratinocytes and mutations in this gene have been associated with bullous congenital ichthyosiform erythroderma. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]
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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=-0.87).
BP6
?
Variant 12-52645289-G-A is Benign according to our data. Variant chr12-52645289-G-A is described in ClinVar as [Benign]. Clinvar id is 309598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
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Synonymous conserved (PhyloP=-1.02 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT2 | NM_000423.3 | c.1650C>T | p.Gly550= | synonymous_variant | 9/9 | ENST00000309680.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT2 | ENST00000309680.4 | c.1650C>T | p.Gly550= | synonymous_variant | 9/9 | 1 | NM_000423.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0218 AC: 3315AN: 151832Hom.: 126 Cov.: 32
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GnomAD3 exomes AF: 0.00593 AC: 1490AN: 251182Hom.: 54 AF XY: 0.00418 AC XY: 568AN XY: 135740
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GnomAD4 exome AF: 0.00269 AC: 3927AN: 1461856Hom.: 129 Cov.: 32 AF XY: 0.00232 AC XY: 1689AN XY: 727238
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GnomAD4 genome ? AF: 0.0219 AC: 3324AN: 151950Hom.: 127 Cov.: 32 AF XY: 0.0218 AC XY: 1619AN XY: 74272
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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 | GeneDx | May 04, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | - - |
KRT2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 04, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Ichthyosis bullosa of Siemens 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
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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