Variant 2-172088141-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_178120.5(DLX1):c.652C>A(p.Pro218Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,610,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

DLX1
NM_178120.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

Variant links:

Genes affected

DLX1 (HGNC:2914): (distal-less homeobox 1) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. The encoded protein is localized to the nucleus where it may function as a transcriptional regulator of signals from multiple TGF-{beta} superfamily members. The encoded protein may play a role in the control of craniofacial patterning and the differentiation and survival of inhibitory neurons in the forebrain. This gene is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 2. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

DLX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029139638).

BS2

High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX1	NM_178120.5 linkuse as main transcript	c.652C>A	p.Pro218Thr	missense_variant	3/3	ENST00000361725.5	NP_835221.2
DLX1	NM_001038493.2 linkuse as main transcript	c.*62C>A		3_prime_UTR_variant	2/2		NP_001033582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX1	ENST00000361725.5 linkuse as main transcript	c.652C>A	p.Pro218Thr	missense_variant	3/3	1	NM_178120.5	ENSP00000354478	P1	P56177-1
DLX1	ENST00000341900.6 linkuse as main transcript	c.*62C>A		3_prime_UTR_variant	2/2	1		ENSP00000341786		P56177-2
DLX1	ENST00000475989.2 linkuse as main transcript	n.726C>A		non_coding_transcript_exon_variant	2/2	2
DLX1	ENST00000550686.1 linkuse as main transcript	n.341C>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000322

AC:

AN:

248152

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

134208

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.0000590

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:

0.00000480

AC:

AN:

1458470

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725508

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.0000451

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000151

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000389

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

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

May 01, 2024

The c.652C>A (p.P218T) alteration is located in exon 3 (coding exon 3) of the DLX1 gene. This alteration results from a C to A substitution at nucleotide position 652, causing the proline (P) at amino acid position 218 to be replaced by a threonine (T). 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

0.053

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.18

Eigen

Benign

-0.21

Eigen_PC

Benign

0.015

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.73

M_CAP

Benign

0.043

MetaRNN

Benign

0.029

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

0.84

REVEL

Benign

0.20

Sift

Benign

0.32

Sift4G

Benign

0.79

Polyphen

0.0

Vest4

0.067

MVP

0.66

MPC

1.3

ClinPred

0.041

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.50

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