chr14-59334082-A-C

Variant names:

• chr14-59334082-A-C
• rs1957409
• NM_001270520.2:c.1968+2162A>C

Variant summary

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

The NM_001270520.2(DAAM1):​c.1968+2162A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,998 control chromosomes in the GnomAD database, including 23,268 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 0.55 (23268 hom., cov: 33)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 10 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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270520.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM1	NM_001270520.2	MANE Select	c.1968+2162A>C		intron	N/A	NP_001257449.1	Q9Y4D1-2
	DAAM1	NM_014992.2		c.1968+2162A>C		intron	N/A	NP_055807.1	Q9Y4D1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM1	ENST00000360909.8	TSL:1 MANE Select	c.1968+2162A>C		intron	N/A	ENSP00000354162.3	Q9Y4D1-2
	DAAM1	ENST00000395125.1	TSL:1	c.1968+2162A>C		intron	N/A	ENSP00000378557.1	Q9Y4D1-1
	DAAM1	ENST00000554459.5	TSL:5	n.187+2162A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83645 AN: 151880 Hom.: 23272 Cov.: 33

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.550 AC: 83670 AN: 151998 Hom.: 23268 Cov.: 33 AF XY: 0.550 AC XY: 40861 AN XY: 74262

African (AFR) AF: 0.506 AC: 20987 AN: 41448

American (AMR) AF: 0.575 AC: 8789 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3468

East Asian (EAS) AF: 0.799 AC: 4135 AN: 5174

South Asian (SAS) AF: 0.605 AC: 2911 AN: 4812

European-Finnish (FIN) AF: 0.532 AC: 5609 AN: 10544

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37601 AN: 67952

Other (OTH) AF: 0.554 AC: 1168 AN: 2110

Alfa AF: 0.558 Hom.: 76624

Bravo AF: 0.555

Asia WGS AF: 0.669 AC: 2324 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.3
DANN	Benign	0.53
PhyloP100		1.8
Mutation Taster		=99/1	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: rs1957409; hg19: chr14-59800800; COSMIC: COSV62840057;