dbSNP rs771359780: DLGAP5:p.Arg821Ile (chr14-55148430-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014750.5(DLGAP5):c.2462G>T(p.Arg821Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R821K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DLGAP5
NM_014750.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.182

Variant links:

Genes affected

DLGAP5 (HGNC:16864): (DLG associated protein 5) Predicted to enable microtubule binding activity. Predicted to be involved in several processes, including centrosome localization; kinetochore assembly; and mitotic spindle organization. Located in several cellular components, including centrosome; cytosol; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

DLGAP5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13724032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP5	NM_014750.5 link	c.2462G>T	p.Arg821Ile	missense_variant	Exon 19 of 19	ENST00000247191.7	NP_055565.3	Q15398-2
DLGAP5	XM_017021840.3 link	c.2462G>T	p.Arg821Ile	missense_variant	Exon 19 of 19		XP_016877329.1	Q15398-2
DLGAP5	NM_001146015.2 link	c.*24G>T		3_prime_UTR_variant	Exon 20 of 20		NP_001139487.1	Q15398-3
DLGAP5	XM_047432016.1 link	c.*24G>T		3_prime_UTR_variant	Exon 20 of 20		XP_047287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP5	ENST00000247191.7 link	c.2462G>T	p.Arg821Ile	missense_variant	Exon 19 of 19	1	NM_014750.5	ENSP00000247191.2		Q15398-2
DLGAP5	ENST00000395425 link	c.*24G>T		3_prime_UTR_variant	Exon 20 of 20	1		ENSP00000378815.2		Q15398-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248940

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.14

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.83

M_CAP

Benign

0.011

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.051

Sift

Uncertain

0.014

Sift4G

Uncertain

0.022

Polyphen

0.91

Vest4

0.40

MutPred

0.31

Loss of disorder (P = 0.0268);

MVP

0.17

MPC

0.21

ClinPred

0.32

GERP RS

-0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over