chr17-7190800-C-CA

Variant names:

• chr17-7190800-C-CA
• NM_001321075.3:c.2082dupT

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_001321075.3(DLG4):​c.2082dupT​(p.Asp695fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DLG4 NM_001321075.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -1.67

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0428 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-7190800-C-CA is Pathogenic according to our data. Variant chr17-7190800-C-CA is described in ClinVar as [Pathogenic]. Clinvar id is 2498102.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.2082dupT	p.Asp695fs	frameshift_variant	Exon 20 of 20	ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399506.9	c.2082dupT	p.Asp695fs	frameshift_variant	Exon 20 of 20	2	NM_001321075.3	ENSP00000382425.2
DLG4	ENST00000648172.8	c.2211dupT	p.Asp738fs	frameshift_variant	Exon 22 of 22			ENSP00000497806.3
DLG4	ENST00000648896.1	c.2181dupT	p.Asp728fs	frameshift_variant	Exon 20 of 20			ENSP00000497546.1
DLG4	ENST00000649520.1	c.1902dupT	p.Asp635fs	frameshift_variant	Exon 19 of 19			ENSP00000497647.1
DLG4	ENST00000491753.2	n.*97dupT		non_coding_transcript_exon_variant	Exon 21 of 21	2		ENSP00000467897.2
DLG4	ENST00000491753.2	n.*97dupT		3_prime_UTR_variant	Exon 21 of 21	2		ENSP00000467897.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual developmental disorder 62 Pathogenic:1

Feb 28, 2023

Tumer Group, Copenhagen University Hospital, Rigshospitalet

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7094119;