17-7202080-A-G

Variant names:

• chr17-7202080-A-G
• rs929229
• NM_001321075.3:c.787+823T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321075.3(DLG4):​c.787+823T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,988 control chromosomes in the GnomAD database, including 37,389 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (37389 hom., cov: 31)
• Consequence: DLG4 NM_001321075.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551
• Publications: 20 publications found

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]

DLG4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual developmental disorder 62

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.787+823T>C		intron_variant	Intron 8 of 19	ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399506.9	c.787+823T>C		intron_variant	Intron 8 of 19	2	NM_001321075.3	ENSP00000382425.2
DLG4	ENST00000648172.9	c.916+823T>C		intron_variant	Intron 10 of 21			ENSP00000497806.3
DLG4	ENST00000648896.1	c.886+823T>C		intron_variant	Intron 8 of 19			ENSP00000497546.1
DLG4	ENST00000649520.1	c.607+823T>C		intron_variant	Intron 7 of 18			ENSP00000497647.1
DLG4	ENST00000648263.1	c.607+823T>C		intron_variant	Intron 6 of 13			ENSP00000498035.1
DLG4	ENST00000451807.7	c.703+823T>C		intron_variant	Intron 7 of 7	5		ENSP00000407918.3
DLG4	ENST00000491753.2	n.916+823T>C		intron_variant	Intron 10 of 20	2		ENSP00000467897.2

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105242 AN: 151870 Hom.: 37329 Cov.: 31

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.693 AC: 105354 AN: 151988 Hom.: 37389 Cov.: 31 AF XY: 0.691 AC XY: 51352 AN XY: 74266

African (AFR) AF: 0.837 AC: 34730 AN: 41476

American (AMR) AF: 0.583 AC: 8898 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2125 AN: 3470

East Asian (EAS) AF: 0.463 AC: 2385 AN: 5156

South Asian (SAS) AF: 0.658 AC: 3166 AN: 4810

European-Finnish (FIN) AF: 0.699 AC: 7372 AN: 10548

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44388 AN: 67956

Other (OTH) AF: 0.691 AC: 1457 AN: 2108

Alfa AF: 0.662 Hom.: 42540

Bravo AF: 0.685

Asia WGS AF: 0.597 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.60
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs929229; hg19: chr17-7105399;