14-58638439-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001079520.2(DACT1):c.237G>C(p.Ala79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000934 in 1,337,040 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (7 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (5 hom.)
• Consequence: DACT1 NM_001079520.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.465

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 14-58638439-G-C is Benign according to our data. Variant chr14-58638439-G-C is described in ClinVar as [Benign]. Clinvar id is 720493.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.465 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00501 (763/152284) while in subpopulation AFR AF= 0.0179 (742/41568). AF 95% confidence interval is 0.0168. There are 7 homozygotes in gnomad4. There are 362 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 751 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DACT1	NM_001079520.2	c.237G>C	p.Ala79=	synonymous_variant	1/4	ENST00000395153.8
DACT1	NM_016651.6	c.237G>C	p.Ala79=	synonymous_variant	1/4
DACT1	NR_046093.2	n.126-2297G>C		intron_variant, non_coding_transcript_variant
DACT1	NR_165650.1	n.126-2297G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DACT1	ENST00000395153.8	c.237G>C	p.Ala79=	synonymous_variant	1/4	5	NM_001079520.2

Frequencies

GnomAD3 genomes AF: 0.00494 AC: 751 AN: 152170 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

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: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00142 AC: 98 AN: 69196 Hom.: 1 AF XY: 0.000850 AC XY: 33 AN XY: 38844

Gnomad AFR exome AF: 0.0197

Gnomad AMR exome AF: 0.000312

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000410 AC: 486 AN: 1184756 Hom.: 5 Cov.: 29 AF XY: 0.000383 AC XY: 219 AN XY: 571380

Gnomad4 AFR exome AF: 0.0168

Gnomad4 AMR exome AF: 0.000547

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000531

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000514

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00501 AC: 763 AN: 152284 Hom.: 7 Cov.: 33 AF XY: 0.00486 AC XY: 362 AN XY: 74474

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00416 Hom.: 0

Bravo AF: 0.00615

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	4.5
Dann	Benign	0.55

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: rs373138468; hg19: chr14-59105157;