rs3004070

chr6-39902176-T-A

Variant summary

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

The NM_001201427.2(DAAM2):c.*139T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 650,104 control chromosomes in the GnomAD database, including 87,402 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 0.51 (19742 hom., cov: 33)
  • Exomes 𝑓: 0.52 (67660 hom.)
• Consequence: DAAM2 NM_001201427.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

Genes affected

DAAM2 (HGNC:18143): (dishevelled associated activator of morphogenesis 2) Predicted to enable actin binding activity and small GTPase binding activity. Predicted to be involved in nervous system development and regulation of Wnt signaling pathway. Predicted to act upstream of or within determination of left/right symmetry. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MOCS1 (HGNC:7190): (molybdenum cofactor synthesis 1) Molybdenum cofactor biosynthesis is a conserved pathway leading to the biological activation of molybdenum. The protein encoded by this gene is involved in this pathway. This gene was originally thought to produce a bicistronic mRNA with the potential to produce two proteins (MOCS1A and MOCS1B) from adjacent open reading frames. However, only the first open reading frame (MOCS1A) has been found to encode a protein from the putative bicistronic mRNA, whereas additional splice variants are likely to produce a fusion between the two open reading frames. This gene is defective in patients with molybdenum cofactor deficiency, type A. A related pseudogene has been identified on chromosome 16. [provided by RefSeq, Nov 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM2	NM_001201427.2	c.*139T>A		3_prime_UTR_variant	25/25	ENST00000274867.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM2	ENST00000274867.9	c.*139T>A		3_prime_UTR_variant	25/25	1	NM_001201427.2	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77089 AN: 151886 Hom.: 19723 Cov.: 33

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.527

GnomAD4 exome AF: 0.517 AC: 257293 AN: 498100 Hom.: 67660 Cov.: 7 AF XY: 0.520 AC XY: 133632 AN XY: 256828

Gnomad4 AFR exome AF: 0.498

Gnomad4 AMR exome AF: 0.511

Gnomad4 ASJ exome AF: 0.545

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.583

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.507 AC: 77137 AN: 152004 Hom.: 19742 Cov.: 33 AF XY: 0.507 AC XY: 37695 AN XY: 74302

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.523

Alfa AF: 0.503 Hom.: 2356

Bravo AF: 0.507

Asia WGS AF: 0.425 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	1.7
Dann	Benign	0.90

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: rs3004070; hg19: chr6-39869952; COSMIC: COSV51321162; COSMIC: COSV51321162;