rs12880248

Positions:

• chr14-59350013-G-A
• chr14-59350013-G-T

Variant summary

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

The NM_001270520.2(DAAM1):​c.2160+2390G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,050 control chromosomes in the GnomAD database, including 1,183 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 0.10 (1183 hom., cov: 31)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.2160+2390G>A		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+2390G>A		intron_variant		1	NM_001270520.2	ENSP00000354162	P1
DAAM1	ENST00000395125.1	c.2190+2390G>A		intron_variant		1		ENSP00000378557
DAAM1	ENST00000553966.5	n.77+2390G>A		intron_variant, non_coding_transcript_variant		2
DAAM1	ENST00000554459.5	n.379+2390G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15425 AN: 151932 Hom.: 1178 Cov.: 31

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.102 AC: 15440 AN: 152050 Hom.: 1183 Cov.: 31 AF XY: 0.101 AC XY: 7527 AN XY: 74298

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.0504

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.106

Alfa AF: 0.128 Hom.: 1121

Bravo AF: 0.108

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.16

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: rs12880248; hg19: chr14-59816731;