17-7218565-T-C
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2
The ENST00000399510.8(DLG4):āc.94A>Gā(p.Ser32Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000253 in 1,564,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.00012 ( 0 hom., cov: 32)
Exomes š: 0.00027 ( 0 hom. )
Consequence
DLG4
ENST00000399510.8 missense
ENST00000399510.8 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 4.10
Genes affected
DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DLG4. . Gene score misZ 4.933 (greater than the threshold 3.09). Trascript score misZ 4.6509 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder, intellectual developmental disorder 62.
BP4
Computational evidence support a benign effect (MetaRNN=0.007270336).
BP6
Variant 17-7218565-T-C is Benign according to our data. Variant chr17-7218565-T-C is described in ClinVar as [Benign]. Clinvar id is 2647321.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLG4 | NM_001365.4 | c.94A>G | p.Ser32Gly | missense_variant | 2/22 | ||
DLG4 | NM_001321074.1 | c.94A>G | p.Ser32Gly | missense_variant | 2/22 | ||
ACADVL | NM_001270447.2 | c.131+747T>C | intron_variant | ||||
DLG4 | NR_135527.1 | n.1295A>G | non_coding_transcript_exon_variant | 2/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLG4 | ENST00000399510.8 | c.94A>G | p.Ser32Gly | missense_variant | 2/22 | 1 | |||
DLG4 | ENST00000648172.8 | c.94A>G | p.Ser32Gly | missense_variant | 2/22 | ||||
ACADVL | ENST00000543245.6 | c.131+747T>C | intron_variant | 2 | |||||
DLG4 | ENST00000491753.2 | c.94A>G | p.Ser32Gly | missense_variant, NMD_transcript_variant | 2/21 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000649 AC: 112AN: 172638Hom.: 0 AF XY: 0.000846 AC XY: 78AN XY: 92194
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GnomAD4 exome AF: 0.000268 AC: 378AN: 1411842Hom.: 0 Cov.: 31 AF XY: 0.000371 AC XY: 259AN XY: 697582
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
DLG4-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 17, 2021 | 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). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | DLG4: PP2, BP4, BS1, BS2 - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Uncertain
.;D
Sift4G
Benign
.;T
Polyphen
B;B
Vest4
0.53
MutPred
Gain of catalytic residue at S32 (P = 0.0244);Gain of catalytic residue at S32 (P = 0.0244);
MVP
0.62
MPC
1.1
ClinPred
T
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at