rs368959516

Variant names:

• chr11-83469202-C-T
• rs368959516
• NM_001142699.3:c.2618G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-83469202-C-T
• chr11-83469202-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001142699.3(DLG2):​c.2618G>A​(p.Arg873Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000145 in 1,602,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: DLG2 NM_001142699.3 missense, splice_region
• Scores: Splicing: ADA: 0.6244
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22033623).

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.2618G>A	p.Arg873Lys	missense splice_region	Exon 25 of 28	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.2600G>A	p.Arg867Lys	missense splice_region	Exon 24 of 27	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.2597G>A	p.Arg866Lys	missense splice_region	Exon 23 of 26	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.2618G>A	p.Arg873Lys	missense splice_region	Exon 25 of 28	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.2303G>A	p.Arg768Lys	missense splice_region	Exon 20 of 23	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.2249G>A	p.Arg750Lys	missense splice_region	Exon 20 of 23	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.0000792 AC: 12 AN: 151430 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000536 AC: 13 AN: 242352 AF XY: 0.0000456

Gnomad AFR exome AF: 0.000132

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000901

Gnomad OTH exome AF: 0.000172

GnomAD4 exome AF: 0.000152 AC: 221 AN: 1450996 Hom.: 0 Cov.: 32 AF XY: 0.000129 AC XY: 93 AN XY: 721474

African (AFR) AF: 0.0000302 AC: 1 AN: 33060

American (AMR) AF: 0.00 AC: 0 AN: 42832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25830

East Asian (EAS) AF: 0.00 AC: 0 AN: 39318

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.000184 AC: 204 AN: 1106800

Other (OTH) AF: 0.000250 AC: 15 AN: 59902

GnomAD4 genome AF: 0.0000792 AC: 12 AN: 151430 Hom.: 0 Cov.: 31 AF XY: 0.0000812 AC XY: 6 AN XY: 73870

African (AFR) AF: 0.0000243 AC: 1 AN: 41200

American (AMR) AF: 0.0000658 AC: 1 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.000131 Hom.: 0

Bravo AF: 0.0000567

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000662 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.025
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-0.55	N
PhyloP100		3.8
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.13	N
REVEL	Benign	0.23
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.018	B
Vest4		0.25
MVP		0.86
MPC		1.7
ClinPred		0.13	T
GERP RS		5.7
Varity_R		0.27
gMVP		0.82
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.62
dbscSNV1_RF	Benign	0.34
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: rs368959516; hg19: chr11-83180245;