6-39856353-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001201427.2(DAAM2):c.51C>T(p.Phe17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000727 in 1,553,546 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (7 hom.)
• Consequence: DAAM2 NM_001201427.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.58

Genes affected

DAAM2 (HGNC:18143): (dishevelled associated activator of morphogenesis 2) Predicted to enable actin binding activity and small GTPase binding activity. Predicted to be involved in nervous system development and regulation of Wnt signaling pathway. Predicted to act upstream of or within determination of left/right symmetry. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 6-39856353-C-T is Benign according to our data. Variant chr6-39856353-C-T is described in ClinVar as [Benign]. Clinvar id is 3053048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.58 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM2	NM_001201427.2	c.51C>T	p.Phe17=	synonymous_variant	2/25	ENST00000274867.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM2	ENST00000274867.9	c.51C>T	p.Phe17=	synonymous_variant	2/25	1	NM_001201427.2	P1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 571 AN: 152222 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

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: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000958 AC: 161 AN: 168012 Hom.: 1 AF XY: 0.000812 AC XY: 73 AN XY: 89880

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000466

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000277

Gnomad OTH exome AF: 0.000477

GnomAD4 exome AF: 0.000398 AC: 557 AN: 1401206 Hom.: 7 Cov.: 31 AF XY: 0.000354 AC XY: 245 AN XY: 692540

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.000793

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000286

Gnomad4 SAS exome AF: 0.0000257

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000305

Gnomad4 OTH exome AF: 0.000860

GnomAD4 genome AF: 0.00376 AC: 573 AN: 152340 Hom.: 3 Cov.: 32 AF XY: 0.00368 AC XY: 274 AN XY: 74498

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00174 Hom.: 0

Bravo AF: 0.00455

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DAAM2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 24, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	6.3
Dann	Benign	0.77

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: rs376650953; hg19: chr6-39824129; COSMIC: COSV51340332;