Variant 6-39867673-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000274867.9(DAAM2):c.592C>T(p.Pro198Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000892 in 1,614,038 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 (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

DAAM2
ENST00000274867.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

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=0.040296555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM2	NM_001201427.2 linkuse as main transcript	c.592C>T	p.Pro198Ser	missense_variant	6/25	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.592C>T	p.Pro198Ser	missense_variant	6/25	1	NM_001201427.2	ENSP00000274867	P1	Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000722

AC:

AN:

249202

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000602

AC:

AN:

1461702

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000368

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000267

Hom.:

Bravo

AF:

0.000465

ESP6500AA

AF:

0.000937

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000908

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.592C>T (p.P198S) alteration is located in exon 6 (coding exon 5) of the DAAM2 gene. This alteration results from a C to T substitution at nucleotide position 592, causing the proline (P) at amino acid position 198 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;D;.;D

Eigen

Benign

0.024

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;.;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.040

T;T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.1

.;L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.8

.;D;D;D

REVEL

Uncertain

0.52

Sift

Benign

0.23

.;T;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.074

.;B;.;B

Vest4

0.27

MVP

0.86

MPC

0.64

ClinPred

0.13

GERP RS

5.5

Varity_R

0.35

gMVP

0.74

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