rs780212257

Variant names:

• chr17-7218244-ACTCT-A
• rs780212257
• ENST00000648172.8:c.152_155delAGAG

Your query was ambiguous. Multiple possible variants found:

• chr17-7218244-ACTCT-A
• chr17-7218244-ACTCT-ACT

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001365.5(DLG4):​c.152_155delAGAG​(p.Glu51ValfsTer30) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: DLG4 NM_001365.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001365.5	c.152_155delAGAG	p.Glu51ValfsTer30	frameshift_variant	Exon 3 of 22		NP_001356.1
DLG4	NM_001321074.1	c.152_155delAGAG	p.Glu51ValfsTer30	frameshift_variant	Exon 3 of 22		NP_001308003.1
ACADVL	NM_001270447.2	c.131+429_131+432delCTCT		intron_variant	Intron 2 of 20		NP_001257376.1
DLG4	NR_135527.1	n.1353_1356delAGAG		non_coding_transcript_exon_variant	Exon 3 of 21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000648172.8	c.152_155delAGAG	p.Glu51ValfsTer30	frameshift_variant	Exon 3 of 22			ENSP00000497806.3
DLG4	ENST00000491753.2	n.152_155delAGAG		non_coding_transcript_exon_variant	Exon 3 of 21	2		ENSP00000467897.2

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs780212257; hg19: chr17-7121563;