chr18-3879209-C-T

Variant names:

• chr18-3879209-C-T
• rs572366902
• NM_004746.4:c.860G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_004746.4(DLGAP1):​c.860G>A​(p.Arg287Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000354 in 1,562,876 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (9 hom.)
• Consequence: DLGAP1 NM_004746.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.81
• Publications: 1 publications found

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

DLGAP1-AS3 (HGNC:27317): (DLGAP1 antisense RNA 3)

LOC124904238 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008782178).
• BP6: Variant 18-3879209-C-T is Benign according to our data. Variant chr18-3879209-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3033733.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004746.4. 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
	DLGAP1	NM_004746.4	MANE Select	c.860G>A	p.Arg287Gln	missense	Exon 4 of 13	NP_004737.2
	DLGAP1	NM_001398525.1		c.860G>A	p.Arg287Gln	missense	Exon 4 of 14	NP_001385454.1
	DLGAP1	NM_001398526.1		c.860G>A	p.Arg287Gln	missense	Exon 4 of 14	NP_001385455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.860G>A	p.Arg287Gln	missense	Exon 4 of 13	ENSP00000316377.3	O14490-1
	DLGAP1	ENST00000498188.5	TSL:1	n.868G>A		non_coding_transcript_exon	Exon 1 of 5
	DLGAP1-AS3	ENST00000577649.1	TSL:1	n.112+918C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000243 AC: 37 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000708 AC: 150 AN: 211976 AF XY: 0.000935

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000143

Gnomad ASJ exome AF: 0.000305

Gnomad EAS exome AF: 0.000119

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000102

Gnomad OTH exome AF: 0.000599

GnomAD4 exome AF: 0.000366 AC: 516 AN: 1410534 Hom.: 9 Cov.: 31 AF XY: 0.000527 AC XY: 367 AN XY: 696220

African (AFR) AF: 0.00 AC: 0 AN: 31758

American (AMR) AF: 0.000108 AC: 4 AN: 37156

Ashkenazi Jewish (ASJ) AF: 0.0000877 AC: 2 AN: 22818

East Asian (EAS) AF: 0.000128 AC: 5 AN: 39156

South Asian (SAS) AF: 0.00596 AC: 464 AN: 77806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51756

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5486

European-Non Finnish (NFE) AF: 0.00000828 AC: 9 AN: 1086590

Other (OTH) AF: 0.000534 AC: 31 AN: 58008

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24 AN XY: 74496

African (AFR) AF: 0.00 AC: 0 AN: 41598

American (AMR) AF: 0.000457 AC: 7 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00581 AC: 28 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000755 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.000685 AC: 83

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DLGAP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PhyloP100		5.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.57	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.41	B
Vest4		0.85
MutPred		0.34		Loss of MoRF binding (P = 0.0325)
MVP		0.84
MPC		1.2
ClinPred		0.063	T
GERP RS		5.5
Varity_R		0.11
gMVP		0.27
Mutation Taster		=96/4	polymorphism

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: rs572366902; hg19: chr18-3879209; COSMIC: COSV59820567; COSMIC: COSV59820567;