Genetic Variant NM_001201427.2:c.7C>T (chr6-39856309-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001201427.2(DAAM2):c.7C>T(p.Pro3Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000523 in 1,532,524 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00054 ( 14 hom. )

Consequence

DAAM2
NM_001201427.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.76

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069828033).

BP6

Variant 6-39856309-C-T is Benign according to our data. Variant chr6-39856309-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3270755.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2 link	c.7C>T	p.Pro3Ser	missense_variant	Exon 2 of 25	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.7C>T	p.Pro3Ser	missense_variant	Exon 2 of 25	1	NM_001201427.2	ENSP00000274867.4		Q86T65-3

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00112

AC:

167

AN:

149246

Hom.:

AF XY:

0.00150

AC XY:

119

AN XY:

79406

show subpopulations

Gnomad AFR exome

AF:

0.000114

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00937

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000541

AC:

746

AN:

1380190

Hom.:

Cov.:

AF XY:

0.000795

AC XY:

541

AN XY:

680656

show subpopulations

Gnomad4 AFR exome

AF:

0.0000655

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00953

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000187

Gnomad4 OTH exome

AF:

0.000647

GnomAD4 genome

AF:

0.000368

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000198

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.000843

AC:

101

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

May 20, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.087

T;T;.;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

T;.;T;T;T

MetaRNN

Benign

0.0070

T;T;T;T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.1

.;M;M;M;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.2

.;N;N;N;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.024

.;D;D;D;D

Sift4G

Benign

0.091

T;T;T;T;T

Polyphen

0.70, 0.98

.;P;.;P;D

Vest4

0.19

MVP

0.47

MPC

0.15

ClinPred

0.082

GERP RS

5.9

Varity_R

0.18

gMVP

0.54

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