Variant 6-39860979-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001201427.2(DAAM2):c.220C>A(p.Pro74Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,613,048 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 1 hom. )

Consequence

DAAM2
NM_001201427.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 2.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024380147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM2	NM_001201427.2 linkuse as main transcript	c.220C>A	p.Pro74Thr	missense_variant	3/25	ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9 linkuse as main transcript	c.220C>A	p.Pro74Thr	missense_variant	3/25	1	NM_001201427.2	ENSP00000274867	P1	Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000848

AC:

AN:

247640

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

134244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000726

Gnomad SAS exome

AF:

0.000199

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000561

AC:

AN:

1460850

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

726580

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000597

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000968

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000171

Hom.:

ExAC

AF:

0.0000745

AC:

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DAAM2-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 2024

The DAAM2 c.220C>A variant is predicted to result in the amino acid substitution p.Pro74Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.073% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Nephrotic syndrome, type 24

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Feb 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;T;.;T;D

Eigen

Benign

-0.029

Eigen_PC

Benign

0.028

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.88

D;.;D;D;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.024

T;T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.8

.;L;L;L;.

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

.;N;N;N;D

REVEL

Benign

0.27

Sift

Benign

0.20

.;T;T;T;D

Sift4G

Benign

0.33

T;T;T;T;D

Polyphen

0.080, 0.98

.;B;.;B;D

Vest4

0.38

MutPred

0.54

Loss of catalytic residue at P73 (P = 0.0121);Loss of catalytic residue at P73 (P = 0.0121);Loss of catalytic residue at P73 (P = 0.0121);Loss of catalytic residue at P73 (P = 0.0121);Loss of catalytic residue at P73 (P = 0.0121);

MVP

0.68

MPC

0.24

ClinPred

0.042

GERP RS

5.3

Varity_R

0.12

gMVP

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over