6-168307788-T-C

Variant names:

• chr6-168307788-T-C
• NM_214462.5:c.1969A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_214462.5(DACT2):​c.1969A>G​(p.Thr657Ala) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DACT2 NM_214462.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.268

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029867887).
• BP6: Variant 6-168307788-T-C is Benign according to our data. Variant chr6-168307788-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2494019.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DACT2	NM_214462.5	c.1969A>G	p.Thr657Ala	missense_variant	Exon 4 of 4	ENST00000366795.4	NP_999627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DACT2	ENST00000366795.4	c.1969A>G	p.Thr657Ala	missense_variant	Exon 4 of 4	2	NM_214462.5	ENSP00000355760.3
DACT2	ENST00000610183.1	c.1459A>G	p.Thr487Ala	missense_variant	Exon 3 of 3	1		ENSP00000476573.1
DACT2	ENST00000607983.1	c.745A>G	p.Thr249Ala	missense_variant	Exon 2 of 2	1		ENSP00000476434.1
DACT2	ENST00000366796.7	c.658+2380A>G		intron_variant	Intron 3 of 5	1		ENSP00000355761.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 06, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.11
DANN	Benign	0.15
DEOGEN2	Benign	0.045	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00050	N
LIST_S2	Benign	0.36	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.030	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.23	N;.;.
REVEL	Benign	0.016
Sift	Benign	1.0	T;.;.
Sift4G	Benign	0.92	T;T;T
Polyphen		0.0080	B;.;.
Vest4		0.010
MutPred		0.28		Loss of phosphorylation at T657 (P = 0.0056);.;.;
MVP		0.014
ClinPred		0.023	T
GERP RS		0.68
Varity_R		0.022
gMVP		0.071

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-168708468;