7-97006051-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCA

Variant names:

• chr7-97006051-GGCAGCA-G
• rs530625473
• NM_005222.4:c.93_98delGCAGCA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005222.4(DLX6):​c.93_98delGCAGCA​(p.Gln32_Gln33del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000298 in 1,582,078 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (1 hom., cov: 29)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: DLX6 NM_005222.4 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 6.66

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-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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX6	NM_005222.4	c.93_98delGCAGCA	p.Gln32_Gln33del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000518156.3	NP_005213.3
DLX6-AS1	NR_015448.1	n.141+7868_141+7873delTGCTGC		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3	c.93_98delGCAGCA	p.Gln32_Gln33del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_005222.4	ENSP00000428480.2

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 71 AN: 150048 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00966

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.0000993

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000134

Gnomad OTH AF: 0.000485

GnomAD3 exomes AF: 0.000796 AC: 151 AN: 189612 Hom.: 1 AF XY: 0.000650 AC XY: 67 AN XY: 103156

Gnomad AFR exome AF: 0.000384

Gnomad AMR exome AF: 0.000315

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00902

Gnomad SAS exome AF: 0.000161

Gnomad FIN exome AF: 0.000117

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000279 AC: 400 AN: 1431934 Hom.: 1 AF XY: 0.000259 AC XY: 184 AN XY: 710086

Gnomad4 AFR exome AF: 0.000275

Gnomad4 AMR exome AF: 0.000292

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00568

Gnomad4 SAS exome AF: 0.000159

Gnomad4 FIN exome AF: 0.0000200

Gnomad4 NFE exome AF: 0.000118

Gnomad4 OTH exome AF: 0.000287

GnomAD4 genome AF: 0.000473 AC: 71 AN: 150144 Hom.: 1 Cov.: 29 AF XY: 0.000518 AC XY: 38 AN XY: 73326

Gnomad4 AFR AF: 0.000195

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00969

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.0000993

Gnomad4 NFE AF: 0.000134

Gnomad4 OTH AF: 0.000482

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Nov 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant, c.93_98del, results in the deletion of 2 amino acid(s) of the DLX6 protein (p.Gln43_Gln44del), 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -

DLX6-related disorder Benign:1

Jun 11, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs530625473; hg19: chr7-96635363;