Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate
The NM_000249.4(MLH1):c.1039-6delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).
MLH1 (HGNC:7127): (mutL homolog 1) The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). [provided by RefSeq, Aug 2017]
Verdict is Likely_benign. Variant got -2 ACMG points.
BP6
Variant 3-37025629-TA-T is Benign according to our data. Variant chr3-37025629-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 679516.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-37025629-TA-T is described in Lovd as [Benign].
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -