rs17834014

Positions:

• chr14-59349308-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001270520.2(DAAM1):​c.2160+1685A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,368 control chromosomes in the GnomAD database, including 376 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 0.062 (376 hom., cov: 33)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.2160+1685A>G		intron_variant		ENST00000360909.8	NP_001257449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.2160+1685A>G		intron_variant		1	NM_001270520.2	ENSP00000354162	P1
DAAM1	ENST00000395125.1	c.2190+1685A>G		intron_variant		1		ENSP00000378557
DAAM1	ENST00000553966.5	n.77+1685A>G		intron_variant, non_coding_transcript_variant		2
DAAM1	ENST00000554459.5	n.379+1685A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9372 AN: 152250 Hom.: 375 Cov.: 33

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0616 AC: 9379 AN: 152368 Hom.: 376 Cov.: 33 AF XY: 0.0607 AC XY: 4520 AN XY: 74514

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0752

Gnomad4 EAS AF: 0.0125

Gnomad4 SAS AF: 0.0513

Gnomad4 FIN AF: 0.0878

Gnomad4 NFE AF: 0.0904

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0840 Hom.: 757

Bravo AF: 0.0568

Asia WGS AF: 0.0510 AC: 176 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.84

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: rs17834014; hg19: chr14-59816026;