rs142038079
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_005546.4(ITK):āc.631G>Cā(p.Val211Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000576 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V211I) has been classified as Uncertain significance.
Frequency
Consequence
NM_005546.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITK | NM_005546.4 | c.631G>C | p.Val211Leu | missense_variant | 6/17 | ENST00000422843.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITK | ENST00000422843.8 | c.631G>C | p.Val211Leu | missense_variant | 6/17 | 1 | NM_005546.4 | P1 | |
ENST00000519375.1 | n.35+1348C>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000289 AC: 44AN: 152154Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251400Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135858
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727240
GnomAD4 genome AF: 0.000289 AC: 44AN: 152272Hom.: 0 Cov.: 31 AF XY: 0.000309 AC XY: 23AN XY: 74452
ClinVar
Submissions by phenotype
Lymphoproliferative syndrome 1 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | ITK NM_005546 exon 6 p.Val211Leu (c.631G>C): This variant has not been reported in the literature but is present in 0.1% (32/24024) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs142038079). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 05, 2022 | The c.631G>C (p.V211L) alteration is located in exon 6 (coding exon 6) of the ITK gene. This alteration results from a G to C substitution at nucleotide position 631, causing the valine (V) at amino acid position 211 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at