chr11-84894629-G-A

Variant names:

• chr11-84894629-G-A
• rs6592211
• NM_001142699.3:c.357+217032C>T

Variant summary

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

The NM_001142699.3(DLG2):​c.357+217032C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,956 control chromosomes in the GnomAD database, including 13,873 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 0.42 (13873 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 5 publications found

Genes affected

DLG2 (HGNC:2901): (discs large MAGUK scaffold protein 2) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. The encoded protein forms a heterodimer with a related family member that 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. Additional transcript variants have been described, but their full-length nature is not known. [provided by RefSeq, Dec 2008]

DLG2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• delayed puberty, self-limited

  Inheritance: AR, AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142699.3. 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
	DLG2	NM_001142699.3	MANE Select	c.357+217032C>T		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.393+259927C>T		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.393+259927C>T		intron	N/A	NP_001338204.1	A0A994J7P1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG2	ENST00000376104.7	TSL:1 MANE Select	c.357+217032C>T		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.42+28448C>T		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.42+28448C>T		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63785 AN: 151838 Hom.: 13858 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.420 AC: 63835 AN: 151956 Hom.: 13873 Cov.: 32 AF XY: 0.424 AC XY: 31514 AN XY: 74268

African (AFR) AF: 0.421 AC: 17448 AN: 41434

American (AMR) AF: 0.307 AC: 4684 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1302 AN: 3470

East Asian (EAS) AF: 0.291 AC: 1503 AN: 5164

South Asian (SAS) AF: 0.369 AC: 1779 AN: 4816

European-Finnish (FIN) AF: 0.596 AC: 6275 AN: 10532

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29285 AN: 67962

Other (OTH) AF: 0.412 AC: 872 AN: 2114

Alfa AF: 0.421 Hom.: 25889

Bravo AF: 0.399

Asia WGS AF: 0.339 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.29
PhyloP100		-0.36
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: rs6592211; hg19: chr11-84605673;