14-58638358-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001079520.2(DACT1):c.156G>A(p.Leu52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000926 in 1,306,308 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00099 (4 hom.)
• Consequence: DACT1 NM_001079520.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.30

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 14-58638358-G-A is Benign according to our data. Variant chr14-58638358-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 712597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.3 with no splicing effect.
• BS2: High AC in GnomAd at 72 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACT1	NM_001079520.2	c.156G>A	p.Leu52=	synonymous_variant	1/4	ENST00000395153.8
DACT1	NM_016651.6	c.156G>A	p.Leu52=	synonymous_variant	1/4
DACT1	NR_046093.2	n.126-2378G>A		intron_variant, non_coding_transcript_variant
DACT1	NR_165650.1	n.126-2378G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACT1	ENST00000395153.8	c.156G>A	p.Leu52=	synonymous_variant	1/4	5	NM_001079520.2

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152064 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

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: 0.000677

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00147 AC: 2 AN: 1362 Hom.: 0 AF XY: 0.00241 AC XY: 2 AN XY: 830

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000986 AC: 1138 AN: 1154136 Hom.: 4 Cov.: 29 AF XY: 0.000997 AC XY: 554 AN XY: 555644

Gnomad4 AFR exome AF: 0.0000430

Gnomad4 AMR exome AF: 0.000459

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.00103

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28 AN XY: 74396

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000677

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000635 Hom.: 0

Bravo AF: 0.000620

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	14
Dann	Uncertain	0.98

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

LitVar

Other links and lift over

dbSNP: rs558640078; hg19: chr14-59105076;