Variant NM_005222.4:c.93_98dupGCAGCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_005222.4(DLX6):c.93_98dupGCAGCA(p.Gln32_Gln33dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0005 in 150,144 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DLX6
NM_005222.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.11

Variant links:

Genes affected

DLX6 (HGNC:2919): (distal-less homeobox 6) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. This family is comprised of at least 6 different members that encode proteins with roles in forebrain and craniofacial development. This gene is in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7. [provided by RefSeq, Jul 2008]

DLX6 links:

DLX6-AS1 (HGNC:37151): (DLX6 antisense RNA 1) Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DLX6-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005222.4

BS2

High AC in GnomAd4 at 75 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX6	NM_005222.4 link	c.93_98dupGCAGCA	p.Gln32_Gln33dup	disruptive_inframe_insertion	Exon 1 of 3	ENST00000518156.3	NP_005213.3	P56179-3
DLX6-AS1	NR_015448.1 link	n.141+7868_141+7873dupTGCTGC		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3 link	c.93_98dupGCAGCA	p.Gln32_Gln33dup	disruptive_inframe_insertion	Exon 1 of 3	1	NM_005222.4	ENSP00000428480.2		P56179-3

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

150048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000265

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000394

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000193

Gnomad OTH

AF:

0.000971

GnomAD3 exomes

AF:

0.000290

AC:

AN:

189612

Hom.:

AF XY:

0.000252

AC XY:

AN XY:

103156

show subpopulations

Gnomad AFR exome

AF:

0.000961

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.000443

Gnomad SAS exome

AF:

0.000403

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.000408

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000277

AC:

396

AN:

1431964

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

200

AN XY:

710102

show subpopulations

Gnomad4 AFR exome

AF:

0.000886

Gnomad4 AMR exome

AF:

0.000462

Gnomad4 ASJ exome

AF:

0.000156

Gnomad4 EAS exome

AF:

0.000392

Gnomad4 SAS exome

AF:

0.000415

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000249

Gnomad4 OTH exome

AF:

0.000372

GnomAD4 genome

AF:

0.000500

AC:

AN:

150144

Hom.:

Cov.:

AF XY:

0.000546

AC XY:

AN XY:

73326

show subpopulations

Gnomad4 AFR

AF:

0.00131

Gnomad4 AMR

AF:

0.000265

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000395

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000193

Gnomad4 OTH

AF:

0.000964

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Oct 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.93_98dup, results in the insertion of 2 amino acid(s) of the DLX6 protein (p.Gln43_Gln44dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DLX6-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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