7-97006051-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

• chr7-97006051-G-GGCAGCAGCA
• rs530625473
• NM_005222.4:c.90_98dupGCAGCAGCA

Variant summary

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

The NM_005222.4(DLX6):​c.90_98dupGCAGCAGCA​(p.Gln31_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 0.000173 in 150,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00017 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLX6 NM_005222.4 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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 26 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.90_98dupGCAGCAGCA	p.Gln31_Gln33dup	disruptive_inframe_insertion	Exon 1 of 3	NP_005213.3
	DLX6-AS1	NR_015448.1		n.141+7865_141+7873dupTGCTGCTGC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX6	ENST00000518156.3	TSL:1 MANE Select	c.90_98dupGCAGCAGCA	p.Gln31_Gln33dup	disruptive_inframe_insertion	Exon 1 of 3	ENSP00000428480.2	P56179-3
	DLX6-AS1	ENST00000458352.5	TSL:1	n.615+5765_615+5773dupTGCTGCTGC		intron	N/A
	DLX6-AS1	ENST00000430027.3	TSL:2	n.141+7865_141+7873dupTGCTGCTGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000173 AC: 26 AN: 150048 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000977

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.000397

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000208

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000844 AC: 16 AN: 189612 AF XY: 0.0000679

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000350

Gnomad ASJ exome AF: 0.000111

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000352

Gnomad NFE exome AF: 0.0000492

Gnomad OTH exome AF: 0.000408

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000125 AC: 179 AN: 1431982 Hom.: 0 Cov.: 34 AF XY: 0.000128 AC XY: 91 AN XY: 710106

African (AFR) AF: 0.0000305 AC: 1 AN: 32742

American (AMR) AF: 0.0000243 AC: 1 AN: 41158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25642

East Asian (EAS) AF: 0.0000523 AC: 2 AN: 38222

South Asian (SAS) AF: 0.0000976 AC: 8 AN: 81958

European-Finnish (FIN) AF: 0.000160 AC: 8 AN: 49986

Middle Eastern (MID) AF: 0.00140 AC: 8 AN: 5722

European-Non Finnish (NFE) AF: 0.000126 AC: 138 AN: 1097382

Other (OTH) AF: 0.000220 AC: 13 AN: 59170

GnomAD4 genome AF: 0.000173 AC: 26 AN: 150048 Hom.: 0 Cov.: 29 AF XY: 0.000123 AC XY: 9 AN XY: 73220

African (AFR) AF: 0.0000977 AC: 4 AN: 40956

American (AMR) AF: 0.0000663 AC: 1 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3450

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5074

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4760

European-Finnish (FIN) AF: 0.000397 AC: 4 AN: 10066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.000208 AC: 14 AN: 67382

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.000292 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (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;