chr6-39856329-T-C

Variant names:

• chr6-39856329-T-C
• rs11965120
• NM_001201427.2:c.27T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001201427.2(DAAM2):​c.27T>C​(p.His9His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,548,998 control chromosomes in the GnomAD database, including 288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 32)
  • Exomes 𝑓: 0.014 (268 hom.)
• Consequence: DAAM2 NM_001201427.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.61

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-39856329-T-C is Benign according to our data. Variant chr6-39856329-T-C is described in ClinVar as [Benign]. Clinvar id is 3060337.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2	c.27T>C	p.His9His	synonymous_variant	Exon 2 of 25	ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9	c.27T>C	p.His9His	synonymous_variant	Exon 2 of 25	1	NM_001201427.2	ENSP00000274867.4

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1859 AN: 152204 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0135 AC: 2240 AN: 165822 Hom.: 32 AF XY: 0.0138 AC XY: 1224 AN XY: 88824

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00854

Gnomad EAS exome AF: 0.0569

Gnomad SAS exome AF: 0.00683

Gnomad FIN exome AF: 0.00454

Gnomad NFE exome AF: 0.0139

Gnomad OTH exome AF: 0.0136

GnomAD4 exome AF: 0.0142 AC: 19792 AN: 1396676 Hom.: 268 Cov.: 31 AF XY: 0.0140 AC XY: 9690 AN XY: 690098

Gnomad4 AFR exome AF: 0.00566

Gnomad4 AMR exome AF: 0.00989

Gnomad4 ASJ exome AF: 0.00772

Gnomad4 EAS exome AF: 0.0756

Gnomad4 SAS exome AF: 0.00695

Gnomad4 FIN exome AF: 0.00530

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0146

GnomAD4 genome AF: 0.0122 AC: 1859 AN: 152322 Hom.: 20 Cov.: 32 AF XY: 0.0118 AC XY: 880 AN XY: 74494

Gnomad4 AFR AF: 0.00539

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.0591

Gnomad4 SAS AF: 0.00973

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00999 Hom.: 11

Bravo AF: 0.0124

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DAAM2-related disorder Benign:1

Feb 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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	-0.52
CADD	Benign	8.5
DANN	Benign	0.62

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: rs11965120; hg19: chr6-39824105;