14-59264527-C-T

Position:

• chr14-59264527-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000360909.8(DAAM1):​c.183+867C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,040 control chromosomes in the GnomAD database, including 13,679 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 0.42 (13678 hom., cov: 32)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: DAAM1 ENST00000360909.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.183+867C>T		intron_variant		ENST00000360909.8	NP_001257449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.183+867C>T		intron_variant		1	NM_001270520.2	ENSP00000354162	P1
DAAM1	ENST00000395125.1	c.183+867C>T		intron_variant		1		ENSP00000378557
DAAM1	ENST00000556596.1	n.1210C>T		non_coding_transcript_exon_variant	2/2	1
DAAM1	ENST00000556135.1	c.183+867C>T		intron_variant		3		ENSP00000450498

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64047 AN: 151912 Hom.: 13661 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.333 AC: 4 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.375

GnomAD4 genome AF: 0.422 AC: 64119 AN: 152028 Hom.: 13678 Cov.: 32 AF XY: 0.424 AC XY: 31512 AN XY: 74310

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.430

Alfa AF: 0.420 Hom.: 7070

Bravo AF: 0.413

Asia WGS AF: 0.364 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.51

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: rs1253005; hg19: chr14-59731245;