NM_000251.3:c.2210+11_2210+22delCTCCTAGTCCCT
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_000251.3(MSH2):c.2210+11_2210+22delCTCCTAGTCCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,460,282 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000251.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251428Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135902
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1460282Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 726624
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
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The variant is found in BR-OV-HEREDIC panel(s). -
not specified Uncertain:1
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Lynch syndrome 1 Uncertain:1
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Hereditary nonpolyposis colorectal neoplasms Benign:1
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Malignant tumor of breast Benign:1
The MSH2 c.2210+11_2210+22del variant was identified in 1 of 42 proband chromosomes (frequency: 0.02) from individuals or families with lynch syndrome. The variant was identified, and most likely located on the same allele, with MSH2 pathogenic variant c.942+3A>T (Ziada-Bouchaar 2017). The variant was also identified in the following databases: dbSNP (ID: rs730881782) as "With other allele", ClinVar (classified as benign by GeneDx; as likely benign by Color Genomics; as uncertain significance by Counsyl), and in Insight Hereditary Tumors (1x). The variant was not identified in COGR, UMD-LSDB, Zhejiang University Database, Mismatch Repair Genes Variant database, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at