dbSNP rs882559: DAAM2:c.2812-12G>C (chr6-39901290-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001201427.2(DAAM2):c.2812-12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,609,308 control chromosomes in the GnomAD database, including 251,444 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 0.59 ( 27107 hom., cov: 32)

Exomes 𝑓: 0.55 ( 224337 hom. )

Consequence

DAAM2
NM_001201427.2 intron

Scores

Splicing: ADA: 0.00003844

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

Publications

12 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen

MOCS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2 link	c.2812-12G>C		intron_variant	Intron 23 of 24	ENST00000274867.9	NP_001188356.1	Q86T65-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9 link	c.2812-12G>C		intron_variant	Intron 23 of 24	1	NM_001201427.2	ENSP00000274867.4		Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

90171

AN:

151926

Hom.:

27077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.690

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.607

GnomAD2 exomes

AF:

0.575

AC:

141725

AN:

246390

AF XY:

0.575

show subpopulations

Gnomad AFR exome

AF:

0.697

Gnomad AMR exome

AF:

0.577

Gnomad ASJ exome

AF:

0.575

Gnomad EAS exome

AF:

0.607

Gnomad FIN exome

AF:

0.531

Gnomad NFE exome

AF:

0.549

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.553

AC:

806256

AN:

1457264

Hom.:

224337

Cov.:

AF XY:

0.555

AC XY:

402455

AN XY:

724838

show subpopulations

African (AFR)

AF:

0.701

AC:

23440

AN:

33450

American (AMR)

AF:

0.578

AC:

25774

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

14881

AN:

25816

East Asian (EAS)

AF:

0.586

AC:

23242

AN:

39680

South Asian (SAS)

AF:

0.618

AC:

52900

AN:

85650

European-Finnish (FIN)

AF:

0.530

AC:

28228

AN:

53236

Middle Eastern (MID)

AF:

0.654

AC:

3755

AN:

5738

European-Non Finnish (NFE)

AF:

0.541

AC:

599364

AN:

1108862

Other (OTH)

AF:

0.576

AC:

34672

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

16839

33678

50518

67357

84196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.594

AC:

90244

AN:

152044

Hom.:

27107

Cov.:

AF XY:

0.593

AC XY:

44106

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.690

AC:

28621

AN:

41474

American (AMR)

AF:

0.584

AC:

8934

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

2013

AN:

3468

East Asian (EAS)

AF:

0.611

AC:

3143

AN:

5140

South Asian (SAS)

AF:

0.615

AC:

2962

AN:

4818

European-Finnish (FIN)

AF:

0.535

AC:

5668

AN:

10586

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.542

AC:

36848

AN:

67958

Other (OTH)

AF:

0.606

AC:

1283

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1880

3759

5639

7518

9398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.488

Hom.:

2544

Bravo

AF:

0.603

Asia WGS

AF:

0.581

AC:

2025

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.7

(source)

DANN

Benign

0.54

PhyloP100

-0.049

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0

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

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rs882559

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over