rs9944927
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000598334.5(DTNA):c.2062G>A(p.Glu688Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,535,714 control chromosomes in the GnomAD database, including 43,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.30 ( 8928 hom., cov: 32)
Exomes 𝑓: 0.21 ( 34516 hom. )
Consequence
DTNA
ENST00000598334.5 missense
ENST00000598334.5 missense
Scores
1
7
Clinical Significance
Conservation
PhyloP100: 1.98
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=1.4859438E-4).
BP6
?
Variant 18-34890327-G-A is Benign according to our data. Variant chr18-34890327-G-A is described in ClinVar as [Benign]. Clinvar id is 137181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-34890327-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.*2593G>A | 3_prime_UTR_variant | 23/23 | ENST00000444659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.*2593G>A | 3_prime_UTR_variant | 23/23 | 5 | NM_001386795.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.297 AC: 45116AN: 151828Hom.: 8893 Cov.: 32
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GnomAD3 exomes AF: 0.202 AC: 27673AN: 136942Hom.: 3634 AF XY: 0.202 AC XY: 15041AN XY: 74366
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GnomAD4 exome AF: 0.212 AC: 293115AN: 1383768Hom.: 34516 Cov.: 33 AF XY: 0.211 AC XY: 144206AN XY: 682832
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GnomAD4 genome ? AF: 0.298 AC: 45218AN: 151946Hom.: 8928 Cov.: 32 AF XY: 0.292 AC XY: 21708AN XY: 74274
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3406
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 2013 | 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. - |
Benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationTaster
Benign
P;P;P;P;P
Sift4G
Uncertain
D
Vest4
MPC
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at