rs397517445
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001386795.1(DTNA):c.148+7A>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000274 in 1,461,212 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
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
DTNA
NM_001386795.1 splice_region, intron
NM_001386795.1 splice_region, intron
Scores
2
Splicing: ADA: 0.00001012
2
Clinical Significance
Conservation
PhyloP100: 3.61
Genes affected
DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 18-34766048-A-G is Benign according to our data. Variant chr18-34766048-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 46415.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.148+7A>G | splice_region_variant, intron_variant | ENST00000444659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.148+7A>G | splice_region_variant, intron_variant | 5 | NM_001386795.1 | P3 | |||
ENST00000596954.1 | n.122-54T>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461212Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726896
GnomAD4 exome
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4
AN:
1461212
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31
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1
AN XY:
726896
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 21, 2012 | 148+7A>G in intron 4 of DTNA: This variant is not expected to have clinical sign ificance because it is not located within the splice consensus sequence. 148+7 A>G in intron 4 of DTNA (allele frequency = n/a) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at