6-39856434-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001201427.2(DAAM2):c.132C>T(p.Asn44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,492,272 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (2 hom.)
• Consequence: DAAM2 NM_001201427.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.190

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 6-39856434-C-T is Benign according to our data. Variant chr6-39856434-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3032413.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.19 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM2	NM_001201427.2	c.132C>T	p.Asn44=	synonymous_variant	2/25	ENST00000274867.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM2	ENST00000274867.9	c.132C>T	p.Asn44=	synonymous_variant	2/25	1	NM_001201427.2	P1

Frequencies

GnomAD3 genomes AF: 0.000276 AC: 42 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000422 AC: 57 AN: 134942 Hom.: 2 AF XY: 0.000471 AC XY: 34 AN XY: 72198

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00326

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000109

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.000187 AC: 251 AN: 1339990 Hom.: 2 Cov.: 31 AF XY: 0.000249 AC XY: 164 AN XY: 658804

Gnomad4 AFR exome AF: 0.000142

Gnomad4 AMR exome AF: 0.000364

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00280

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000276

Gnomad4 OTH exome AF: 0.000289

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74452

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.0000947 Hom.: 0

Bravo AF: 0.000374

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DAAM2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 07, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.8
Dann	Benign	0.66

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

Other links and lift over

dbSNP: rs535365178; hg19: chr6-39824210; COSMIC: COSV51418175;