chr14-59350013-G-A

Variant names:

• chr14-59350013-G-A
• rs12880248
• NM_001270520.2:c.2160+2390G>A

Variant summary

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

The ENST00000360909.8(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 ENST00000360909.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360909.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM1	NM_001270520.2	MANE Select	c.2160+2390G>A		intron	N/A	NP_001257449.1
	DAAM1	NM_014992.2		c.2190+2390G>A		intron	N/A	NP_055807.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM1	ENST00000360909.8	TSL:1 MANE Select	c.2160+2390G>A		intron	N/A	ENSP00000354162.3
	DAAM1	ENST00000395125.1	TSL:1	c.2190+2390G>A		intron	N/A	ENSP00000378557.1
	DAAM1	ENST00000553966.5	TSL:2	n.77+2390G>A		intron	N/A

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

African (AFR) AF: 0.0258 AC: 1070 AN: 41480

American (AMR) AF: 0.190 AC: 2912 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0960 AC: 333 AN: 3470

East Asian (EAS) AF: 0.123 AC: 633 AN: 5140

South Asian (SAS) AF: 0.236 AC: 1135 AN: 4808

European-Finnish (FIN) AF: 0.0504 AC: 534 AN: 10586

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8439 AN: 67958

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.126 Hom.: 1487

Bravo AF: 0.108

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.16
PhyloP100		-1.1
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: rs12880248; hg19: chr14-59816731;