rs2504086

Positions:

• chr6-39878361-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.1361-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,607,492 control chromosomes in the GnomAD database, including 272,058 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 0.58 (25802 hom., cov: 32)
  • Exomes 𝑓: 0.58 (246256 hom.)
• Consequence: DAAM2 NM_001201427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM2	NM_001201427.2	c.1361-43A>G		intron_variant		ENST00000274867.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM2	ENST00000274867.9	c.1361-43A>G		intron_variant		1	NM_001201427.2	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88039 AN: 151822 Hom.: 25768 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.582

GnomAD3 exomes AF: 0.605 AC: 146265 AN: 241708 Hom.: 44750 AF XY: 0.608 AC XY: 79586 AN XY: 130980

Gnomad AFR exome AF: 0.562

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.579

Gnomad EAS exome AF: 0.799

Gnomad SAS exome AF: 0.687

Gnomad FIN exome AF: 0.607

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.580 AC: 843764 AN: 1455552 Hom.: 246256 Cov.: 39 AF XY: 0.583 AC XY: 421604 AN XY: 723372

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.570

Gnomad4 ASJ exome AF: 0.575

Gnomad4 EAS exome AF: 0.737

Gnomad4 SAS exome AF: 0.678

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.594

GnomAD4 genome AF: 0.580 AC: 88121 AN: 151940 Hom.: 25802 Cov.: 32 AF XY: 0.583 AC XY: 43323 AN XY: 74254

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.587

Alfa AF: 0.574 Hom.: 43528

Bravo AF: 0.578

Asia WGS AF: 0.737 AC: 2567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.21
DANN	Benign	0.67

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: rs2504086; hg19: chr6-39846137;