7-97006064-G-GCAGCAGCAGCAA

Variant names:

• chr7-97006064-G-GCAGCAGCAGCAA
• rs754232631
• NM_005222.4:c.99_110dupACAGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_005222.4(DLX6):​c.99_110dupACAGCAGCAGCA​(p.Gln34_Gln37dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000132 in 151,146 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000077 (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: 3.77
• 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 -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005222.4

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.99_110dupACAGCAGCAGCA	p.Gln34_Gln37dup	disruptive_inframe_insertion	Exon 1 of 3	NP_005213.3
	DLX6-AS1	NR_015448.1		n.141+7849_141+7860dupTTGCTGCTGCTG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX6	ENST00000518156.3	TSL:1 MANE Select	c.99_110dupACAGCAGCAGCA	p.Gln34_Gln37dup	disruptive_inframe_insertion	Exon 1 of 3	ENSP00000428480.2	P56179-3
	DLX6-AS1	ENST00000458352.5	TSL:1	n.615+5749_615+5760dupTTGCTGCTGCTG		intron	N/A
	DLX6-AS1	ENST00000430027.3	TSL:2	n.141+7849_141+7860dupTTGCTGCTGCTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151146 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000106 AC: 2 AN: 189542 AF XY: 0.0000194

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000249

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000771 AC: 11 AN: 1426926 Hom.: 0 Cov.: 34 AF XY: 0.0000127 AC XY: 9 AN XY: 706996

African (AFR) AF: 0.0000306 AC: 1 AN: 32640

American (AMR) AF: 0.0000250 AC: 1 AN: 40002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25616

East Asian (EAS) AF: 0.00 AC: 0 AN: 37684

South Asian (SAS) AF: 0.00 AC: 0 AN: 81654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000822 AC: 9 AN: 1095192

Other (OTH) AF: 0.00 AC: 0 AN: 59072

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151146 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 73808

African (AFR) AF: 0.0000243 AC: 1 AN: 41206

American (AMR) AF: 0.00 AC: 0 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67694

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 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		3.8
Mutation Taster		=64/36	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs754232631; hg19: chr7-96635376;