rs745986379

Variant names:

• chr6-39856384-C-T
• rs745986379
• NM_001201427.2:c.82C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001201427.2(DAAM2):​c.82C>T​(p.Arg28Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000773 in 1,552,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000081 (0 hom.)
• Consequence: DAAM2 NM_001201427.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15183026).

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.82C>T	p.Arg28Trp	missense	Exon 2 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.82C>T	p.Arg28Trp	missense	Exon 2 of 25	NP_056160.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.82C>T	p.Arg28Trp	missense	Exon 2 of 25	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.82C>T	p.Arg28Trp	missense	Exon 2 of 25	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000405961.3	TSL:1	c.82C>T	p.Arg28Trp	missense	Exon 2 of 3	ENSP00000384637.3	F2Z2Q2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000124 AC: 21 AN: 168802 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000680

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000814 AC: 114 AN: 1400018 Hom.: 0 Cov.: 31 AF XY: 0.0000910 AC XY: 63 AN XY: 692108

African (AFR) AF: 0.00 AC: 0 AN: 31006

American (AMR) AF: 0.00 AC: 0 AN: 36178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24762

East Asian (EAS) AF: 0.0000867 AC: 3 AN: 34612

South Asian (SAS) AF: 0.000630 AC: 49 AN: 77806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.0000500 AC: 54 AN: 1080922

Other (OTH) AF: 0.000138 AC: 8 AN: 58092

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74474

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000914 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	0.0022	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.1
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.022	D
Polyphen		0.97	D
Vest4		0.34
MutPred		0.45		Loss of disorder (P = 0.0182)
MVP		0.56
MPC		0.59
ClinPred		0.50	T
GERP RS		5.2
Varity_R		0.25
gMVP		0.45
Mutation Taster		=73/27	polymorphism

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: rs745986379; hg19: chr6-39824160; COSMIC: COSV51341513;