7-97006081-AGCAGCAGCAGCAGCAGCAACAGCAACA-C

Position:

• chr7-97006081-AGCAGCAGCAGCAGCAGCAACAGCAACA-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The ENST00000518156.3(DLX6):​c.104_131delinsC​(p.Gln35_Gln44delinsPro) variant causes a protein altering change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q35Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: DLX6 ENST00000518156.3 protein_altering
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in ENST00000518156.3

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX6	NM_005222.4	c.104_131delinsC	p.Gln35_Gln44delinsPro	protein_altering_variant	1/3	ENST00000518156.3	NP_005213.3
DLX6-AS1	NR_015448.1	n.141+7817_141+7844delinsG		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3	c.104_131delinsC	p.Gln35_Gln44delinsPro	protein_altering_variant	1/3	1	NM_005222.4	ENSP00000428480	P1
DLX6-AS1	ENST00000430027.3	n.141+7817_141+7844delinsG		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 29

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 29

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

Dec 08, 2021

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with DLX6-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.104_131delinsC, is a complex sequence change that results in the deletion of 10 and insertion of 1 amino acid(s) in the DLX6 protein (p.Gln35_Gln44delinsPro). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-96635393;