8-1549232-A-C

Position:

• chr8-1549232-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001346810.2(DLGAP2):​c.779A>C​(p.Asp260Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLGAP2 NM_001346810.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.44

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34732455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP2	NM_001346810.2	c.779A>C	p.Asp260Ala	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.779A>C	p.Asp260Ala	missense_variant	5/15	5	NM_001346810.2	ENSP00000489774
DLGAP2	ENST00000520901.5	c.590A>C	p.Asp197Ala	missense_variant	1/10	1		ENSP00000430563
DLGAP2	ENST00000421627.7	c.776A>C	p.Asp259Ala	missense_variant	5/15	5		ENSP00000400258
DLGAP2	ENST00000612087.1	c.539A>C	p.Asp180Ala	missense_variant	2/11	5		ENSP00000484215	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.6	.;M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.55	T
REVEL	Benign	0.15
Sift4G	Benign	0.084	.;.;T
Polyphen		0.54	.;P;.
Vest4		0.60
MutPred		0.17		.;Gain of MoRF binding (P = 0.0221);.;
MVP		0.17
MPC		0.15
ClinPred		0.89	D
GERP RS		5.4
Varity_R		0.27
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-1497398;