rs397516400
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000432.4(MYL2):c.274+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000051 in 1,587,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000432.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYL2 | NM_000432.4 | c.274+8C>T | splice_region_variant, intron_variant | ENST00000228841.15 | |||
MYL2 | NM_001406745.1 | c.232+8C>T | splice_region_variant, intron_variant | ||||
MYL2 | NM_001406916.1 | c.217+8C>T | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYL2 | ENST00000228841.15 | c.274+8C>T | splice_region_variant, intron_variant | 1 | NM_000432.4 | P1 | |||
MYL2 | ENST00000548438.1 | c.232+8C>T | splice_region_variant, intron_variant | 3 | |||||
MYL2 | ENST00000663220.1 | c.217+8C>T | splice_region_variant, intron_variant | ||||||
MYL2 | ENST00000549029.1 | n.105+8C>T | splice_region_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000140 AC: 21AN: 149742Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251424Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135898
GnomAD4 exome AF: 0.0000417 AC: 60AN: 1437632Hom.: 0 Cov.: 30 AF XY: 0.0000307 AC XY: 22AN XY: 716640
GnomAD4 genome AF: 0.000140 AC: 21AN: 149742Hom.: 0 Cov.: 32 AF XY: 0.000137 AC XY: 10AN XY: 72972
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 29, 2018 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 06, 2012 | 274+8C>T in intron 4 of MYL2: This variant is not expected to have clinical sign ificance because it is not located within the splice consensus sequence. 274+8C >T in intron 4 of MYL2 (allele frequency = n/a) - |
Hypertrophic cardiomyopathy 10 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
MYL2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at