Variant 14-55154639-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014750.5(DLGAP5):c.2041T>A(p.Phe681Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,614,088 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 1 hom. )

Consequence

DLGAP5
NM_014750.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0450

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005155951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP5	NM_014750.5 linkuse as main transcript	c.2041T>A	p.Phe681Ile	missense_variant	15/19	ENST00000247191.7	NP_055565.3	Q15398-2
DLGAP5	NM_001146015.2 linkuse as main transcript	c.2041T>A	p.Phe681Ile	missense_variant	15/20		NP_001139487.1	Q15398-3
DLGAP5	XM_017021840.3 linkuse as main transcript	c.2041T>A	p.Phe681Ile	missense_variant	15/19		XP_016877329.1	Q15398-2
DLGAP5	XM_047432016.1 linkuse as main transcript	c.2041T>A	p.Phe681Ile	missense_variant	15/20		XP_047287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP5	ENST00000247191.7 linkuse as main transcript	c.2041T>A	p.Phe681Ile	missense_variant	15/19	1	NM_014750.5	ENSP00000247191.2		Q15398-2
DLGAP5	ENST00000395425.6 linkuse as main transcript	c.2041T>A	p.Phe681Ile	missense_variant	15/20	1		ENSP00000378815.2		Q15398-3

Frequencies

GnomAD3 genomes

AF:

0.000966

AC:

147

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00171

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00118

AC:

296

AN:

251268

Hom.:

AF XY:

0.00126

AC XY:

171

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00176

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00178

AC:

2595

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

1365

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00206

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.000965

AC:

147

AN:

152318

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00115

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00127

AC:

154

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00190

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

Jan 12, 2024

The c.2041T>A (p.F681I) alteration is located in exon 15 (coding exon 14) of the DLGAP5 gene. This alteration results from a T to A substitution at nucleotide position 2041, causing the phenylalanine (F) at amino acid position 681 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.0

DANN

Benign

0.84

DEOGEN2

Benign

0.075

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.22

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.32

N;N

REVEL

Benign

0.014

Sift

Benign

0.36

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.0010

.;B

Vest4

0.17

MVP

0.048

MPC

0.086

ClinPred

0.0048

GERP RS

0.20

Varity_R

0.029

gMVP

0.088

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over