rs375777526

Variant names:

• chr17-7191976-C-A
• rs375777526
• NM_001365.5:c.2022G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7191976-C-A
• chr17-7191976-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001321075.3(DLG4):​c.1893G>T​(p.Ser631Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S631S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLG4 NM_001321075.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321075.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	NM_001365.5	MANE Plus Clinical	c.2022G>T	p.Ser674Ser	synonymous	Exon 20 of 22	NP_001356.1	P78352-2
	DLG4	NM_001321075.3	MANE Select	c.1893G>T	p.Ser631Ser	synonymous	Exon 18 of 20	NP_001308004.1	P78352-1
	DLG4	NM_001321074.1		c.2013G>T	p.Ser671Ser	synonymous	Exon 20 of 22	NP_001308003.1	B9EGL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	ENST00000648172.9	MANE Plus Clinical	c.2022G>T	p.Ser674Ser	synonymous	Exon 20 of 22	ENSP00000497806.3	P78352-2
	DLG4	ENST00000399506.9	TSL:2 MANE Select	c.1893G>T	p.Ser631Ser	synonymous	Exon 18 of 20	ENSP00000382425.2	P78352-1
	DLG4	ENST00000399510.8	TSL:1	c.2013G>T	p.Ser671Ser	synonymous	Exon 20 of 22	ENSP00000382428.3	B9EGL1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1308922 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 641716

African (AFR) AF: 0.00 AC: 0 AN: 27598

American (AMR) AF: 0.00 AC: 0 AN: 25060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18896

East Asian (EAS) AF: 0.00 AC: 0 AN: 33608

South Asian (SAS) AF: 0.00 AC: 0 AN: 62112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5102

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1035088

Other (OTH) AF: 0.00 AC: 0 AN: 53234

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.2
DANN	Benign	0.86
PhyloP100		-2.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs375777526; hg19: chr17-7095295;