rs3004067

Variant names:

• chr6-39897271-T-C
• rs3004067
• NM_001201427.2:c.2607T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-39897271-T-C
• chr6-39897271-T-A
• chr6-39897271-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001201427.2(DAAM2):​c.2607T>C​(p.Ala869Ala) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.68 (35542 hom., cov: 31)
  • Exomes 𝑓: 0.63 (289662 hom.)
• Consequence: DAAM2 NM_001201427.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.13
• Publications: 24 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 -14 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 VariationId is 3059909.Status of the report is no_assertion_criteria_provided, 0 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201427.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	NM_001201427.2	MANE Select	c.2607T>C	p.Ala869Ala	synonymous	Exon 21 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.2607T>C	p.Ala869Ala	synonymous	Exon 21 of 25	NP_056160.2
	DAAM2-AS1	NR_125831.1		n.110A>G		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.2607T>C	p.Ala869Ala	synonymous	Exon 21 of 25	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.2607T>C	p.Ala869Ala	synonymous	Exon 21 of 25	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000631498.1	TSL:1	n.3302T>C		non_coding_transcript_exon	Exon 5 of 9

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

GnomAD2 exomes AF: 0.670 AC: 166891 AN: 249060 AF XY: 0.671

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 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

African (AFR) AF: 0.788 AC: 26228 AN: 33268

American (AMR) AF: 0.620 AC: 27712 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 18170 AN: 26076

East Asian (EAS) AF: 0.849 AC: 33662 AN: 39652

South Asian (SAS) AF: 0.744 AC: 64019 AN: 86030

European-Finnish (FIN) AF: 0.666 AC: 35540 AN: 53336

Middle Eastern (MID) AF: 0.731 AC: 4207 AN: 5752

European-Non Finnish (NFE) AF: 0.601 AC: 662154 AN: 1102076

Other (OTH) AF: 0.660 AC: 39584 AN: 59980

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

African (AFR) AF: 0.776 AC: 32193 AN: 41466

American (AMR) AF: 0.637 AC: 9727 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2421 AN: 3464

East Asian (EAS) AF: 0.873 AC: 4497 AN: 5154

South Asian (SAS) AF: 0.743 AC: 3576 AN: 4812

European-Finnish (FIN) AF: 0.689 AC: 7288 AN: 10570

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41118 AN: 67972

Other (OTH) AF: 0.691 AC: 1458 AN: 2110

Alfa AF: 0.637 Hom.: 49669

Bravo AF: 0.684

Asia WGS AF: 0.787 AC: 2737 AN: 3478

EpiCase AF: 0.631

EpiControl AF: 0.632

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DAAM2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-2.1
Mutation Taster		=98/2	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: rs3004067; hg19: chr6-39865047; COSMIC: COSV51302190; COSMIC: COSV51302190;