6-39897271-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001201427.2(DAAM2):c.2607T>C(p.Ala869=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 1,602,868 control chromosomes in the GnomAD database, including 325,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35542 hom., cov: 31)
  • Exomes 𝑓: 0.63 (289662 hom.)
• Consequence: DAAM2 NM_001201427.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.13

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]

DAAM2-AS1 (HGNC:40830): (DAAM2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-39897271-T-C is Benign according to our data. Variant chr6-39897271-T-C is described in ClinVar as [Benign]. Clinvar id is 3059909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM2	NM_001201427.2	c.2607T>C	p.Ala869=	synonymous_variant	21/25	ENST00000274867.9
DAAM2-AS1	NR_125831.1	n.110A>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM2	ENST00000274867.9	c.2607T>C	p.Ala869=	synonymous_variant	21/25	1	NM_001201427.2	P1
DAAM2-AS1	ENST00000606829.1			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103085 AN: 151898 Hom.: 35495 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.687

GnomAD3 exomes AF: 0.670 AC: 166891 AN: 249060 Hom.: 56977 AF XY: 0.671 AC XY: 90637 AN XY: 135126

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.617

Gnomad ASJ exome AF: 0.698

Gnomad EAS exome AF: 0.883

Gnomad SAS exome AF: 0.750

Gnomad FIN exome AF: 0.675

Gnomad NFE exome AF: 0.613

Gnomad OTH exome AF: 0.647

GnomAD4 exome AF: 0.628 AC: 911276 AN: 1450852 Hom.: 289662 Cov.: 30 AF XY: 0.632 AC XY: 456320 AN XY: 722486

Gnomad4 AFR exome AF: 0.788

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.697

Gnomad4 EAS exome AF: 0.849

Gnomad4 SAS exome AF: 0.744

Gnomad4 FIN exome AF: 0.666

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.660

GnomAD4 genome AF: 0.679 AC: 103182 AN: 152016 Hom.: 35542 Cov.: 31 AF XY: 0.685 AC XY: 50876 AN XY: 74292

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.691

Alfa AF: 0.633 Hom.: 39812

Bravo AF: 0.684

Asia WGS AF: 0.787 AC: 2737 AN: 3478

EpiCase AF: 0.631

EpiControl AF: 0.632

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

Oct 17, 2019

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	-0.77
Cadd	Benign	1.4
Dann	Benign	0.66

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: rs3004067; hg19: chr6-39865047; COSMIC: COSV51302190; COSMIC: COSV51302190;