Variant 7-44058145-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001014436.3(DBNL):c.569G>A(p.Arg190His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000356 in 1,404,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

DBNL
NM_001014436.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

DBNL (HGNC:2696): (drebrin like) Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DBNL links:

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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 rank	MANE	Protein	UniProt
DBNL	NM_001014436.3 link	c.569G>A	p.Arg190His	missense_variant	Exon 7 of 13	ENST00000448521.6	NP_001014436.1	Q9UJU6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DBNL	ENST00000448521.6 link	c.569G>A	p.Arg190His	missense_variant	Exon 7 of 13	1	NM_001014436.3	ENSP00000411701.1		Q9UJU6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000614

AC:

AN:

162740

Hom.:

AF XY:

0.00

AC XY:

AN XY:

86400

show subpopulations

Gnomad AFR exome

AF:

0.000108

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1404602

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

693324

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

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:

0.00000369

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000876

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.569G>A (p.R190H) alteration is located in exon 7 (coding exon 7) of the DBNL gene. This alteration results from a G to A substitution at nucleotide position 569, causing the arginine (R) at amino acid position 190 to be replaced by a histidine (H). 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

0.18

BayesDel_addAF

Benign

-0.0030

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.64

D;.;.;.;T;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.44

T;T;T;T;T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Pathogenic

2.9

M;.;.;.;.;M;M

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-4.2

D;D;D;D;D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.0010

D;D;D;D;D;D;D

Sift4G

Uncertain

0.053

T;T;T;T;T;T;T

Polyphen

1.0

D;.;.;.;D;D;D

Vest4

0.48

MutPred

0.31

Loss of helix (P = 0.0104);.;.;.;.;Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);

MVP

0.79

MPC

0.49

ClinPred

0.99

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.62

gMVP

0.48

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over