chr6-168307972-C-T

Variant names:

• chr6-168307972-C-T
• rs183650899
• NM_214462.5:c.1785G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_214462.5(DACT2):​c.1785G>A​(p.Ala595Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00364 in 1,551,042 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (16 hom.)
• Consequence: DACT2 NM_214462.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -8.30
• Publications: 1 publications found

Genes affected

DACT2 (HGNC:21231): (dishevelled binding antagonist of beta catenin 2) Predicted to enable several functions, including beta-catenin binding activity; delta-catenin binding activity; and protein kinase C binding activity. Predicted to be involved in several processes, including epithelial cell morphogenesis; inner medullary collecting duct development; and negative regulation of nodal signaling pathway. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-168307972-C-T is Benign according to our data. Variant chr6-168307972-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-8.3 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_214462.5. 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
	DACT2	NM_214462.5	MANE Select	c.1785G>A	p.Ala595Ala	synonymous	Exon 4 of 4	NP_999627.2	Q5SW24-1
	DACT2	NM_001286350.2		c.1275G>A	p.Ala425Ala	synonymous	Exon 3 of 3	NP_001273279.1	Q5SW24-2
	DACT2	NM_001286351.2		c.658+2196G>A		intron	N/A	NP_001273280.1	Q5SW24-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACT2	ENST00000366795.4	TSL:2 MANE Select	c.1785G>A	p.Ala595Ala	synonymous	Exon 4 of 4	ENSP00000355760.3	Q5SW24-1
	DACT2	ENST00000610183.1	TSL:1	c.1275G>A	p.Ala425Ala	synonymous	Exon 3 of 3	ENSP00000476573.1	Q5SW24-2
	DACT2	ENST00000607983.1	TSL:1	c.561G>A	p.Ala187Ala	synonymous	Exon 2 of 2	ENSP00000476434.1	Q5SW24-3

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 390 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000892

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00256 AC: 391 AN: 152698 AF XY: 0.00260

Gnomad AFR exome AF: 0.000769

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.00686

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000331

Gnomad NFE exome AF: 0.00337

Gnomad OTH exome AF: 0.00858

GnomAD4 exome AF: 0.00376 AC: 5253 AN: 1398738 Hom.: 16 Cov.: 75 AF XY: 0.00385 AC XY: 2657 AN XY: 689938

African (AFR) AF: 0.00114 AC: 36 AN: 31594

American (AMR) AF: 0.00238 AC: 85 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00656 AC: 165 AN: 25156

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35730

South Asian (SAS) AF: 0.00162 AC: 128 AN: 79228

European-Finnish (FIN) AF: 0.000287 AC: 14 AN: 48828

Middle Eastern (MID) AF: 0.0129 AC: 73 AN: 5658

European-Non Finnish (NFE) AF: 0.00421 AC: 4537 AN: 1078872

Other (OTH) AF: 0.00367 AC: 213 AN: 57976

GnomAD4 genome AF: 0.00256 AC: 390 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.00232 AC XY: 173 AN XY: 74468

African (AFR) AF: 0.000890 AC: 37 AN: 41580

American (AMR) AF: 0.00379 AC: 58 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00368 AC: 250 AN: 68012

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00376 Hom.: 1

Bravo AF: 0.00266

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.068
DANN	Benign	0.61
PhyloP100		-8.3
Mutation Taster		=100/0	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: rs183650899; hg19: chr6-168708652; COSMIC: COSV64694306;