chr14-59199216-C-T

Variant names:

• chr14-59199216-C-T
• rs8016570
• NM_001270520.2:c.-38+10448C>T

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+10448C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,066 control chromosomes in the GnomAD database, including 21,509 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 0.53 (21509 hom., cov: 33)
• Consequence: DAAM1 NM_001270520.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAAM1	NM_001270520.2	c.-38+10448C>T		intron_variant	Intron 1 of 24	ENST00000360909.8	NP_001257449.1
DAAM1	XM_005267430.3	c.-38+10448C>T		intron_variant	Intron 1 of 25		XP_005267487.1
DAAM1	XM_005267431.2	c.-38+10302C>T		intron_variant	Intron 1 of 25		XP_005267488.1
DAAM1	XM_047431135.1	c.-38+10302C>T		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+10448C>T		intron_variant	Intron 1 of 24	1	NM_001270520.2	ENSP00000354162.3
DAAM1	ENST00000556596.1	n.123+10448C>T		intron_variant	Intron 1 of 1	1
DAAM1	ENST00000556135.1	c.-38+10448C>T		intron_variant	Intron 1 of 2	3		ENSP00000450498.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80708 AN: 151948 Hom.: 21501 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.531 AC: 80742 AN: 152066 Hom.: 21509 Cov.: 33 AF XY: 0.530 AC XY: 39401 AN XY: 74326

African (AFR) AF: 0.513 AC: 21256 AN: 41454

American (AMR) AF: 0.575 AC: 8788 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1896 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3322 AN: 5180

South Asian (SAS) AF: 0.602 AC: 2903 AN: 4822

European-Finnish (FIN) AF: 0.492 AC: 5195 AN: 10558

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35611 AN: 67974

Other (OTH) AF: 0.546 AC: 1155 AN: 2116

Alfa AF: 0.535 Hom.: 68373

Bravo AF: 0.539

Asia WGS AF: 0.620 AC: 2154 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	0.31
DANN	Benign	0.43
PhyloP100		-0.72
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: rs8016570; hg19: chr14-59665934;