17-7188331-T-C

Variant names:

• chr17-7188331-T-C
• rs314253
• NM_001321075.3:c.*2377A>G

Variant summary

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

The NM_001321075.3(DLG4):​c.*2377A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,036 control chromosomes in the GnomAD database, including 10,494 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 0.37 (10494 hom., cov: 31)
• Consequence: DLG4 NM_001321075.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716
• Publications: 92 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.*2377A>G		3_prime_UTR_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.*2377A>G		3_prime_UTR_variant	Exon 20 of 20	2	NM_001321075.3	ENSP00000382425.2
DLG4	ENST00000648172.9	c.*2377A>G		3_prime_UTR_variant	Exon 22 of 22			ENSP00000497806.3

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55886 AN: 151918 Hom.: 10478 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.368 AC: 55956 AN: 152036 Hom.: 10494 Cov.: 31 AF XY: 0.373 AC XY: 27729 AN XY: 74322

African (AFR) AF: 0.378 AC: 15677 AN: 41480

American (AMR) AF: 0.428 AC: 6535 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 963 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2444 AN: 5170

South Asian (SAS) AF: 0.257 AC: 1237 AN: 4818

European-Finnish (FIN) AF: 0.424 AC: 4477 AN: 10552

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23538 AN: 67962

Other (OTH) AF: 0.333 AC: 703 AN: 2114

Alfa AF: 0.350 Hom.: 44200

Bravo AF: 0.374

Asia WGS AF: 0.356 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.46
PhyloP100		-0.72

Splicing

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

Other links and lift over

dbSNP: rs314253; hg19: chr17-7091650;