rs2242449

Variant names:

• chr17-7192188-C-A
• rs2242449
• NM_001365.5:c.1996-186G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7192188-C-A
• chr17-7192188-C-T
• chr17-7192188-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321075.3(DLG4):​c.1867-186G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 284,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: DLG4 NM_001321075.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 14 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000279812 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).

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.1996-186G>T		intron	N/A	NP_001356.1	P78352-2
	DLG4	NM_001321075.3	MANE Select	c.1867-186G>T		intron	N/A	NP_001308004.1	P78352-1
	DLG4	NM_001321074.1		c.1987-186G>T		intron	N/A	NP_001308003.1	B9EGL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	ENST00000648172.9	MANE Plus Clinical	c.1996-186G>T		intron	N/A	ENSP00000497806.3	P78352-2
	DLG4	ENST00000399506.9	TSL:2 MANE Select	c.1867-186G>T		intron	N/A	ENSP00000382425.2	P78352-1
	DLG4	ENST00000399510.8	TSL:1	c.1987-186G>T		intron	N/A	ENSP00000382428.3	B9EGL1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000351 AC: 1 AN: 284616 Hom.: 0 Cov.: 2 AF XY: 0.00000680 AC XY: 1 AN XY: 147060

African (AFR) AF: 0.00 AC: 0 AN: 7594

American (AMR) AF: 0.00 AC: 0 AN: 9372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9818

East Asian (EAS) AF: 0.00 AC: 0 AN: 23272

South Asian (SAS) AF: 0.00 AC: 0 AN: 11856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1478

European-Non Finnish (NFE) AF: 0.00000557 AC: 1 AN: 179668

Other (OTH) AF: 0.00 AC: 0 AN: 18306

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 7995

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		-0.022

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: rs2242449; hg19: chr17-7095507;