rs527543903

Variant names:

• chr6-39856322-G-A
• rs527543903
• NM_001201427.2:c.20G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001201427.2(DAAM2):​c.20G>A​(p.Ser7Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000024 in 1,543,144 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 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: DAAM2 NM_001201427.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026350737).

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.20G>A	p.Ser7Asn	missense	Exon 2 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.20G>A	p.Ser7Asn	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.20G>A	p.Ser7Asn	missense	Exon 2 of 25	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.20G>A	p.Ser7Asn	missense	Exon 2 of 25	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000405961.3	TSL:1	c.20G>A	p.Ser7Asn	missense	Exon 2 of 3	ENSP00000384637.3	F2Z2Q2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000313 AC: 5 AN: 159850 AF XY: 0.0000234

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000856

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000433

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000252 AC: 35 AN: 1390808 Hom.: 0 Cov.: 31 AF XY: 0.0000204 AC XY: 14 AN XY: 686922

African (AFR) AF: 0.00 AC: 0 AN: 30796

American (AMR) AF: 0.0000285 AC: 1 AN: 35140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23818

East Asian (EAS) AF: 0.00 AC: 0 AN: 34810

South Asian (SAS) AF: 0.00 AC: 0 AN: 75768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50364

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5560

European-Non Finnish (NFE) AF: 0.0000306 AC: 33 AN: 1076918

Other (OTH) AF: 0.00 AC: 0 AN: 57634

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

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

Alfa AF: 0.0000368 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000333 AC: 4

ClinVar

ClinVar submissions as Germline

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	0.079
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.016
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.95	N
REVEL	Uncertain	0.31
Sift	Benign	0.26	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.062
MutPred		0.24		Loss of phosphorylation at S7 (P = 0.0421)
MVP		0.54
MPC		0.14
ClinPred		0.11	T
GERP RS		5.9
Varity_R		0.17
gMVP		0.42
Mutation Taster		=75/25	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: rs527543903; hg19: chr6-39824098;