Genetic Variant DAAM2:p.Ser925Ser (chr6-39900172-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001201427.2(DAAM2):c.2775C>G(p.Ser925Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S925S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DAAM2
NM_001201427.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.966

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 links:

DAAM2-AS1 (HGNC:40830): (DAAM2 antisense RNA 1)

DAAM2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=-0.966 with no splicing effect.

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.2775C>G	p.Ser925Ser	synonymous	Exon 23 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.2772C>G	p.Ser924Ser	synonymous	Exon 23 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.2775C>G	p.Ser925Ser	synonymous	Exon 23 of 25	ENSP00000274867.4	Q86T65-3
DAAM2	ENST00000538976.5	TSL:1	c.2772C>G	p.Ser924Ser	synonymous	Exon 23 of 25	ENSP00000437808.1	Q86T65-4
DAAM2	ENST00000631498.1	TSL:1	n.3470C>G		non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455652

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723472

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33264

American (AMR)

AF:

0.00

AC:

AN:

44132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25962

East Asian (EAS)

AF:

0.00

AC:

AN:

39306

South Asian (SAS)

AF:

0.00

AC:

AN:

84700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109280

Other (OTH)

AF:

0.00

AC:

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.3

(source)

DANN

Benign

0.76

PhyloP100

-0.97

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

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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