rs2504787

Positions:

• chr6-39864335-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201427.2(DAAM2):​c.259-98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 892,692 control chromosomes in the GnomAD database, including 163,306 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28865 hom., cov: 32)
  • Exomes 𝑓: 0.60 (134441 hom.)
• Consequence: DAAM2 NM_001201427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM2	NM_001201427.2	c.259-98A>G		intron_variant		ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9	c.259-98A>G		intron_variant		1	NM_001201427.2	ENSP00000274867	P1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93410 AN: 151894 Hom.: 28841 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.600 AC: 444519 AN: 740680 Hom.: 134441 AF XY: 0.603 AC XY: 230835 AN XY: 383022

Gnomad4 AFR exome AF: 0.666

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.522

Gnomad4 SAS exome AF: 0.685

Gnomad4 FIN exome AF: 0.612

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.619

GnomAD4 genome AF: 0.615 AC: 93474 AN: 152012 Hom.: 28865 Cov.: 32 AF XY: 0.616 AC XY: 45807 AN XY: 74310

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.630

Alfa AF: 0.592 Hom.: 3842

Bravo AF: 0.616

Asia WGS AF: 0.602 AC: 2097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.38

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: rs2504787; hg19: chr6-39832111; COSMIC: COSV51302053; COSMIC: COSV51302053;