chr8-1548974-A-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001346810.2(DLGAP2):āc.521A>Gā(p.Asp174Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
DLGAP2
NM_001346810.2 missense
NM_001346810.2 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 8.59
Genes affected
DLGAP2 (HGNC:2906): (DLG associated protein 2) The product of this gene is a membrane-associated protein that may play a role in synapse organization and signalling in neuronal cells. This gene is biallelically expressed in the brain, however, only the paternal allele is expressed in the testis (PMID:18055845). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jun 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DLGAP2 | NM_001346810.2 | c.521A>G | p.Asp174Gly | missense_variant | 5/15 | ENST00000637795.2 | NP_001333739.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DLGAP2 | ENST00000637795.2 | c.521A>G | p.Asp174Gly | missense_variant | 5/15 | 5 | NM_001346810.2 | ENSP00000489774 | ||
DLGAP2 | ENST00000520901.5 | c.332A>G | p.Asp111Gly | missense_variant | 1/10 | 1 | ENSP00000430563 | |||
DLGAP2 | ENST00000421627.7 | c.518A>G | p.Asp173Gly | missense_variant | 5/15 | 5 | ENSP00000400258 | |||
DLGAP2 | ENST00000612087.1 | c.281A>G | p.Asp94Gly | missense_variant | 2/11 | 5 | ENSP00000484215 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1446832Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 720292
GnomAD4 exome
AF:
AC:
2
AN:
1446832
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
720292
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2023 | The c.281A>G (p.D94G) alteration is located in exon 2 (coding exon 1) of the DLGAP2 gene. This alteration results from a A to G substitution at nucleotide position 281, causing the aspartic acid (D) at amino acid position 94 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Benign
.;.;T
Polyphen
0.98
.;D;.
Vest4
0.84
MutPred
0.45
.;Gain of catalytic residue at D173 (P = 0.0068);.;
MVP
0.22
MPC
0.16
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.