chr14-59352956-T-G

Variant names:

• chr14-59352956-T-G
• rs12878070
• NM_001270520.2:c.2267+324T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270520.2(DAAM1):​c.2267+324T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 149,824 control chromosomes in the GnomAD database, including 13,541 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13541 hom., cov: 27)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 3 publications found

Genes affected

DAAM1 (HGNC:18142): (dishevelled associated activator of morphogenesis 1) Cell motility, adhesion, cytokinesis, and other functions of the cell cortex are mediated by reorganization of the actin cytoskeleton and several formin homology (FH) proteins have been associated with these processes. The protein encoded by this gene contains two FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. A key regulator of cytoskeletal architecture, the small GTPase Rho, is activated during development by Wnt/Fz signaling to control cell polarity and movement. The protein encoded by this gene is thought to function as a scaffolding protein for the Wnt-induced assembly of a disheveled (Dvl)-Rho complex. This protein also promotes the nucleation and elongation of new actin filaments and regulates cell growth through the stabilization of microtubules. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.2267+324T>G		intron_variant	Intron 18 of 24	ENST00000360909.8	NP_001257449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.2267+324T>G		intron_variant	Intron 18 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000395125.1	c.2297+324T>G		intron_variant	Intron 18 of 24	1		ENSP00000378557.1
DAAM1	ENST00000553966.5	n.184+324T>G		intron_variant	Intron 2 of 7	2
DAAM1	ENST00000554459.5	n.486+324T>G		intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes AF: 0.393 AC: 58842 AN: 149716 Hom.: 13542 Cov.: 27

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 58846 AN: 149824 Hom.: 13541 Cov.: 27 AF XY: 0.405 AC XY: 29561 AN XY: 72984

African (AFR) AF: 0.171 AC: 6964 AN: 40678

American (AMR) AF: 0.408 AC: 6131 AN: 15036

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3466

East Asian (EAS) AF: 0.839 AC: 4290 AN: 5116

South Asian (SAS) AF: 0.491 AC: 2310 AN: 4700

European-Finnish (FIN) AF: 0.615 AC: 6098 AN: 9916

Middle Eastern (MID) AF: 0.262 AC: 76 AN: 290

European-Non Finnish (NFE) AF: 0.452 AC: 30595 AN: 67640

Other (OTH) AF: 0.378 AC: 788 AN: 2082

Alfa AF: 0.431 Hom.: 6703

Bravo AF: 0.370

Asia WGS AF: 0.629 AC: 2183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.63
PhyloP100		0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12878070; hg19: chr14-59819674;