Genetic Variant DAAM1:n.1210C>T (chr14-59264527-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000556596.1(DAAM1):n.1210C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,040 control chromosomes in the GnomAD database, including 13,679 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 0.42 ( 13678 hom., cov: 32)

Exomes 𝑓: 0.33 ( 1 hom. )

Consequence

DAAM1
ENST00000556596.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480

Publications

5 publications found

Variant links:

Genes affected

DAAM1 (HGNC:18142): (dishevelled associated activator of morphogenesis 1) Cell motility, adhesion, cytokinesis, and other functions of the cell cortex are mediated by reorganization of the actin cytoskeleton and several formin homology (FH) proteins have been associated with these processes. The protein encoded by this gene contains two FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. A key regulator of cytoskeletal architecture, the small GTPase Rho, is activated during development by Wnt/Fz signaling to control cell polarity and movement. The protein encoded by this gene is thought to function as a scaffolding protein for the Wnt-induced assembly of a disheveled (Dvl)-Rho complex. This protein also promotes the nucleation and elongation of new actin filaments and regulates cell growth through the stabilization of microtubules. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2012]

DAAM1 links:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2 link	c.183+867C>T		intron_variant	Intron 2 of 24	ENST00000360909.8	NP_001257449.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
DAAM1	ENST00000556596.1 link	n.1210C>T	non_coding_transcript_exon_variant	Exon 2 of 2	1
DAAM1	ENST00000360909.8 link	c.183+867C>T	intron_variant	Intron 2 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000395125.1 link	c.183+867C>T	intron_variant	Intron 1 of 24	1		ENSP00000378557.1
DAAM1	ENST00000556135.1 link	c.183+867C>T	intron_variant	Intron 2 of 2	3		ENSP00000450498.1

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64047

AN:

151912

Hom.:

13661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.427

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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:

0.422

AC:

64119

AN:

152028

Hom.:

13678

Cov.:

AF XY:

0.424

AC XY:

31512

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.377

AC:

15638

AN:

41442

American (AMR)

AF:

0.413

AC:

6310

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

1621

AN:

3472

East Asian (EAS)

AF:

0.336

AC:

1742

AN:

5178

South Asian (SAS)

AF:

0.400

AC:

1929

AN:

4820

European-Finnish (FIN)

AF:

0.477

AC:

5031

AN:

10554

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.447

AC:

30358

AN:

67958

Other (OTH)

AF:

0.430

AC:

909

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1914

3827

5741

7654

9568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.422

Hom.:

7825

Bravo

AF:

0.413

Asia WGS

AF:

0.364

AC:

1269

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

(source)

DANN

Benign

0.51

PhyloP100

-0.048

Mutation Taster

=100/0

polymorphism (auto)

(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

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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