7-97006051-GGCAGCAGCA-G

Position:

• chr7-97006051-GGCAGCAGCA-G

Variant summary

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

The ENST00000518156.3(DLX6):​c.90_98del​(p.Gln42_Gln44del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000398 in 1,582,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000060 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: DLX6 ENST00000518156.3 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX6	NM_005222.4	c.90_98del	p.Gln42_Gln44del	inframe_deletion	1/3	ENST00000518156.3	NP_005213.3
DLX6-AS1	NR_015448.1	n.141+7865_141+7873del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3	c.90_98del	p.Gln42_Gln44del	inframe_deletion	1/3	1	NM_005222.4	ENSP00000428480	P1
DLX6-AS1	ENST00000430027.3	n.141+7865_141+7873del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000600 AC: 9 AN: 150048 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000742

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000377 AC: 54 AN: 1431998 Hom.: 0 AF XY: 0.0000394 AC XY: 28 AN XY: 710120

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.0000243

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000523

Gnomad4 SAS exome AF: 0.0000854

Gnomad4 FIN exome AF: 0.000160

Gnomad4 NFE exome AF: 0.0000282

Gnomad4 OTH exome AF: 0.0000507

GnomAD4 genome AF: 0.0000600 AC: 9 AN: 150048 Hom.: 0 Cov.: 29 AF XY: 0.0000546 AC XY: 4 AN XY: 73220

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000199

Gnomad4 NFE AF: 0.0000742

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 02, 2023

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. This variant is not present in population databases (gnomAD no frequency). This variant, c.90_98del, results in the deletion of 3 amino acid(s) of the DLX6 protein (p.Gln42_Gln44del), but otherwise preserves the integrity of the reading frame. -

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;