7-97006051-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCA

Variant names:

• chr7-97006051-GGCA-G
• rs530625473
• NM_005222.4:c.96_98delGCA

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_005222.4(DLX6):​c.96_98delGCA​(p.Gln33del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000329 in 1,572,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: DLX6 NM_005222.4 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.05
• Publications: 1 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: Benign. The variant received -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005222.4
• BP6: Variant 7-97006051-GGCA-G is Benign according to our data. Variant chr7-97006051-GGCA-G is described in ClinVar as Benign. ClinVar VariationId is 1660081.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 48 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_98delGCA	p.Gln33del	disruptive_inframe_deletion	Exon 1 of 3	NP_005213.3
	DLX6-AS1	NR_015448.1		n.141+7871_141+7873delTGC		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_98delGCA	p.Gln33del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000428480.2	P56179-3
	DLX6-AS1	ENST00000458352.5	TSL:1	n.615+5771_615+5773delTGC		intron	N/A
	DLX6-AS1	ENST00000430027.3	TSL:2	n.141+7871_141+7873delTGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000320 AC: 48 AN: 150010 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000977

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000265

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: 0.0000594

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00266 AC: 504 AN: 189612 AF XY: 0.00289

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.00186

Gnomad ASJ exome AF: 0.00145

Gnomad EAS exome AF: 0.00325

Gnomad FIN exome AF: 0.00287

Gnomad NFE exome AF: 0.00317

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.000330 AC: 469 AN: 1422350 Hom.: 0 AF XY: 0.000353 AC XY: 249 AN XY: 705228

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00151 AC: 49 AN: 32378

American (AMR) AF: 0.000763 AC: 31 AN: 40638

Ashkenazi Jewish (ASJ) AF: 0.000236 AC: 6 AN: 25384

East Asian (EAS) AF: 0.000689 AC: 26 AN: 37726

South Asian (SAS) AF: 0.000433 AC: 35 AN: 80840

European-Finnish (FIN) AF: 0.00132 AC: 65 AN: 49344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.000218 AC: 238 AN: 1091656

Other (OTH) AF: 0.000324 AC: 19 AN: 58708

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000320 AC: 48 AN: 150106 Hom.: 0 Cov.: 29 AF XY: 0.000314 AC XY: 23 AN XY: 73300

African (AFR) AF: 0.000974 AC: 40 AN: 41058

American (AMR) AF: 0.000265 AC: 4 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5058

South Asian (SAS) AF: 0.00 AC: 0 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10050

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

European-Non Finnish (NFE) AF: 0.0000594 AC: 4 AN: 67364

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00306 Hom.: 0

Bravo AF: 0.000351

ClinVar

ClinVar submissions

Significance: Benign

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		4.0
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: COSV50292937; COSMIC: COSV50292937;