7-97006051-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

• chr7-97006051-G-GGCA
• rs530625473
• NM_005222.4:c.96_98dupGCA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_005222.4(DLX6):​c.96_98dupGCA​(p.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 0.001 in 1,582,026 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. Q33Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 29)
  • Exomes 𝑓: 0.00089 (1 hom.)
• Consequence: DLX6 NM_005222.4 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 B:1
• Conservation: PhyloP100: 2.11
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005222.4
• BS2: High AC in GnomAd4 at 308 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005222.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX6	NM_005222.4	MANE Select	c.96_98dupGCA	p.Gln33dup	disruptive_inframe_insertion	Exon 1 of 3	NP_005213.3
	DLX6-AS1	NR_015448.1		n.141+7871_141+7873dupTGC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX6	ENST00000518156.3	TSL:1 MANE Select	c.96_98dupGCA	p.Gln33dup	disruptive_inframe_insertion	Exon 1 of 3	ENSP00000428480.2	P56179-3
	DLX6-AS1	ENST00000458352.5	TSL:1	n.615+5771_615+5773dupTGC		intron	N/A
	DLX6-AS1	ENST00000430027.3	TSL:2	n.141+7871_141+7873dupTGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 309 AN: 150048 Hom.: 2 Cov.: 29

Gnomad AFR AF: 0.00544

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00199

Gnomad ASJ AF: 0.000870

Gnomad EAS AF: 0.000394

Gnomad SAS AF: 0.00147

Gnomad FIN AF: 0.0000993

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000594

Gnomad OTH AF: 0.00146

GnomAD2 exomes AF: 0.000849 AC: 161 AN: 189612 AF XY: 0.000785

Gnomad AFR exome AF: 0.00308

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.000223

Gnomad EAS exome AF: 0.000591

Gnomad FIN exome AF: 0.000176

Gnomad NFE exome AF: 0.000479

Gnomad OTH exome AF: 0.00123

GnomAD4 exome AF: 0.000893 AC: 1279 AN: 1431882 Hom.: 1 Cov.: 34 AF XY: 0.000887 AC XY: 630 AN XY: 710042

African (AFR) AF: 0.00422 AC: 138 AN: 32734

American (AMR) AF: 0.00117 AC: 48 AN: 41156

Ashkenazi Jewish (ASJ) AF: 0.000156 AC: 4 AN: 25640

East Asian (EAS) AF: 0.000706 AC: 27 AN: 38222

South Asian (SAS) AF: 0.00142 AC: 116 AN: 81952

European-Finnish (FIN) AF: 0.000420 AC: 21 AN: 49984

Middle Eastern (MID) AF: 0.00210 AC: 12 AN: 5718

European-Non Finnish (NFE) AF: 0.000779 AC: 855 AN: 1097310

Other (OTH) AF: 0.000980 AC: 58 AN: 59166

GnomAD4 genome AF: 0.00205 AC: 308 AN: 150144 Hom.: 2 Cov.: 29 AF XY: 0.00183 AC XY: 134 AN XY: 73326

African (AFR) AF: 0.00543 AC: 223 AN: 41066

American (AMR) AF: 0.00199 AC: 30 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.000870 AC: 3 AN: 3450

East Asian (EAS) AF: 0.000395 AC: 2 AN: 5058

South Asian (SAS) AF: 0.00126 AC: 6 AN: 4758

European-Finnish (FIN) AF: 0.0000993 AC: 1 AN: 10066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000594 AC: 40 AN: 67372

Other (OTH) AF: 0.00145 AC: 3 AN: 2074

Alfa AF: 0.000255 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	-	1	DLX6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=54/46	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs530625473; hg19: chr7-96635363; COSMIC: COSV50295348; COSMIC: COSV50295348;