rs2504787

Variant names:

• chr6-39864335-A-G
• rs2504787
• NM_001201427.2:c.259-98A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2	c.259-98A>G		intron_variant	Intron 3 of 24	ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9	c.259-98A>G		intron_variant	Intron 3 of 24	1	NM_001201427.2	ENSP00000274867.4

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

African (AFR) AF: 0.666 AC: 12350 AN: 18534

American (AMR) AF: 0.598 AC: 16657 AN: 27872

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 12192 AN: 17816

East Asian (EAS) AF: 0.522 AC: 17131 AN: 32802

South Asian (SAS) AF: 0.685 AC: 40694 AN: 59450

European-Finnish (FIN) AF: 0.612 AC: 28930 AN: 47298

Middle Eastern (MID) AF: 0.664 AC: 2130 AN: 3210

European-Non Finnish (NFE) AF: 0.587 AC: 292261 AN: 497876

Other (OTH) AF: 0.619 AC: 22174 AN: 35822

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

African (AFR) AF: 0.661 AC: 27409 AN: 41468

American (AMR) AF: 0.596 AC: 9109 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2385 AN: 3468

East Asian (EAS) AF: 0.574 AC: 2963 AN: 5162

South Asian (SAS) AF: 0.674 AC: 3249 AN: 4822

European-Finnish (FIN) AF: 0.623 AC: 6580 AN: 10560

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39571 AN: 67940

Other (OTH) AF: 0.630 AC: 1329 AN: 2110

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
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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