NM_001270520.2:c.-38+3305A>C

Variant names:

• chr14-59192073-A-C
• rs1252906
• NM_001270520.2:c.-38+3305A>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.-38+3305A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,758 control chromosomes in the GnomAD database, including 1,419 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 0.13 (1419 hom., cov: 30)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.-38+3305A>C		intron_variant	Intron 1 of 24	ENST00000360909.8	NP_001257449.1
DAAM1	XM_005267430.3	c.-38+3305A>C		intron_variant	Intron 1 of 25		XP_005267487.1
DAAM1	XM_005267431.2	c.-38+3159A>C		intron_variant	Intron 1 of 25		XP_005267488.1
DAAM1	XM_047431135.1	c.-38+3159A>C		intron_variant	Intron 1 of 24		XP_047287091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM1	ENST00000360909.8	c.-38+3305A>C		intron_variant	Intron 1 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000556596.1	n.123+3305A>C		intron_variant	Intron 1 of 1	1
DAAM1	ENST00000556135.1	c.-38+3305A>C		intron_variant	Intron 1 of 2	3		ENSP00000450498.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19397 AN: 151640 Hom.: 1419 Cov.: 30

Gnomad AFR AF: 0.0933

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.128 AC: 19406 AN: 151758 Hom.: 1419 Cov.: 30 AF XY: 0.129 AC XY: 9579 AN XY: 74122

African (AFR) AF: 0.0934 AC: 3861 AN: 41360

American (AMR) AF: 0.117 AC: 1791 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3464

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5170

South Asian (SAS) AF: 0.131 AC: 630 AN: 4800

European-Finnish (FIN) AF: 0.188 AC: 1970 AN: 10472

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10143 AN: 67934

Other (OTH) AF: 0.149 AC: 314 AN: 2106

Alfa AF: 0.0943 Hom.: 169

Bravo AF: 0.118

Asia WGS AF: 0.0610 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.60
DANN	Benign	0.79
PhyloP100		-0.078
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1252906; hg19: chr14-59658791;