NM_001079520.2:c.2029G>T

Variant names:

• chr14-58646763-G-T
• NM_001079520.2:c.2029G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001079520.2(DACT1):​c.2029G>T​(p.Ala677Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DACT1 NM_001079520.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.667
• Publications: 0 publications found

Genes affected

DACT1 (HGNC:17748): (dishevelled binding antagonist of beta catenin 1) The protein encoded by this gene belongs to the dapper family, characterized by the presence of PDZ-binding motif at the C-terminus. It interacts with, and positively regulates dishevelled-mediated signaling pathways during development. Depletion of this mRNA from xenopus embryos resulted in loss of notochord and head structures, and mice lacking this gene died shortly after birth from severe posterior malformations. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

LINC01500 (HGNC:51166): (long intergenic non-protein coding RNA 1500)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061915398).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079520.2. 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
	DACT1	NM_001079520.2	MANE Select	c.2029G>T	p.Ala677Ser	missense	Exon 4 of 4	NP_001072988.1	Q9NYF0-2
	DACT1	NM_016651.6		c.2140G>T	p.Ala714Ser	missense	Exon 4 of 4	NP_057735.2
	DACT1	NR_046093.2		n.1809G>T		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DACT1	ENST00000395153.8	TSL:5 MANE Select	c.2029G>T	p.Ala677Ser	missense	Exon 4 of 4	ENSP00000378582.3	Q9NYF0-2
	DACT1	ENST00000335867.4	TSL:1	c.2140G>T	p.Ala714Ser	missense	Exon 4 of 4	ENSP00000337439.4	Q9NYF0-1
	DACT1	ENST00000707126.1		c.2029G>T	p.Ala677Ser	missense	Exon 4 of 4	ENSP00000516754.1	Q9NYF0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	DACT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.8
DANN	Benign	0.80
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.67
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.020
Sift	Benign	0.19	T
Sift4G	Benign	0.22	T
Polyphen		0.0050	B
Vest4		0.10
MutPred		0.18		Gain of glycosylation at A714 (P = 0.0017)
MVP		0.39
MPC		0.17
ClinPred		0.048	T
GERP RS		0.79
Varity_R		0.038
gMVP		0.098
Mutation Taster		=91/9	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

hg19: chr14-59113481; COSMIC: COSV60019545; COSMIC: COSV60019545;