22-28689124-A-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_007194.4(CHEK2):c.1542+11T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,568,954 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_007194.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0159 AC: 2413AN: 152182Hom.: 81 Cov.: 32
GnomAD3 exomes AF: 0.00401 AC: 935AN: 233208Hom.: 35 AF XY: 0.00297 AC XY: 380AN XY: 128106
GnomAD4 exome AF: 0.00160 AC: 2271AN: 1416654Hom.: 72 Cov.: 27 AF XY: 0.00137 AC XY: 972AN XY: 706994
GnomAD4 genome AF: 0.0159 AC: 2416AN: 152300Hom.: 81 Cov.: 32 AF XY: 0.0152 AC XY: 1130AN XY: 74460
ClinVar
Submissions by phenotype
not specified Benign:5
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not provided Benign:3
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Familial cancer of breast Benign:3
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Hereditary cancer-predisposing syndrome Benign:2
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General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance -
Li-Fraumeni syndrome 2 Benign:1
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CHEK2-related cancer predisposition Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Malignant tumor of breast Benign:1
The CHEK2 c.1542+11T>A variant was not identified in the literature nor was it identified in the Cosmic, MutDB or Zhejiang Colon Cancer databases. The variant was identified in the following databases: dbSNP (ID: rs17881716) as "With Likely benign allele", in ClinVar (classified as benign 2x, likely benign 2x), and Clinvitae (classified as benign 2x, likely benign 2x). The variant was identified in control databases in 1364 of 259656 chromosomes (43 homozygous) at a frequency of 0.005 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: African in 1294 of 22484 chromosomes (freq: 0.06). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. -
Hereditary breast ovarian cancer syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at