rs777856703

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001201427.2(DAAM2):c.2915G>A(p.Arg972Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,613,570 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R972W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DAAM2
NM_001201427.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Publications

0 publications found

Variant links:

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 links:

MOCS1 (HGNC:7190): (molybdenum cofactor synthesis 1) Molybdenum cofactor biosynthesis is a conserved pathway leading to the biological activation of molybdenum. The protein encoded by this gene is involved in this pathway. This gene was originally thought to produce a bicistronic mRNA with the potential to produce two proteins (MOCS1A and MOCS1B) from adjacent open reading frames. However, only the first open reading frame (MOCS1A) has been found to encode a protein from the putative bicistronic mRNA, whereas additional splice variants are likely to produce a fusion between the two open reading frames. This gene is defective in patients with molybdenum cofactor deficiency, type A. A related pseudogene has been identified on chromosome 16. [provided by RefSeq, Nov 2017]

MOCS1 Gene-Disease associations (from GenCC):

sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

MOCS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2582473).

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.2915G>A	p.Arg972Gln	missense	Exon 24 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.2912G>A	p.Arg971Gln	missense	Exon 24 of 25	NP_056160.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.2915G>A	p.Arg972Gln	missense	Exon 24 of 25	ENSP00000274867.4	Q86T65-3
DAAM2	ENST00000538976.5	TSL:1	c.2912G>A	p.Arg971Gln	missense	Exon 24 of 25	ENSP00000437808.1	Q86T65-4
DAAM2	ENST00000631498.1	TSL:1	n.3610G>A		non_coding_transcript_exon	Exon 8 of 9

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

248674

AF XY:

0.0000222

show subpopulations

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:

0.00000887

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461444

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53174

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111852

Other (OTH)

AF:

0.0000166

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41422

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.016

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.49

PhyloP100

4.2

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.13

Sift

Benign

0.24

Sift4G

Benign

0.15

Polyphen

0.41

Vest4

0.37

MutPred

0.30

Loss of MoRF binding (P = 0.0213)

MVP

0.61

MPC

0.17

ClinPred

0.70

GERP RS

3.7

Varity_R

0.23

gMVP

0.47

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over