rs3004070

Variant names:

• chr6-39902176-T-A
• rs3004070
• ENST00000631498.1:n.4041T>A

Variant summary

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

The ENST00000631498.1(DAAM2):​n.4041T>A variant causes a non coding transcript exon 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 ENST00000631498.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 11 publications found

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]

MOCS1 Gene-Disease associations (from GenCC):

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DAAM2	NM_001201427.2	c.*139T>A		3_prime_UTR_variant	Exon 25 of 25	ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9	c.*139T>A		3_prime_UTR_variant	Exon 25 of 25	1	NM_001201427.2	ENSP00000274867.4

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

African (AFR) AF: 0.498 AC: 6226 AN: 12504

American (AMR) AF: 0.511 AC: 7919 AN: 15500

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 7161 AN: 13132

East Asian (EAS) AF: 0.353 AC: 9915 AN: 28108

South Asian (SAS) AF: 0.583 AC: 22435 AN: 38452

European-Finnish (FIN) AF: 0.519 AC: 15217 AN: 29334

Middle Eastern (MID) AF: 0.590 AC: 1217 AN: 2062

European-Non Finnish (NFE) AF: 0.521 AC: 173083 AN: 332130

Other (OTH) AF: 0.525 AC: 14120 AN: 26878

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

African (AFR) AF: 0.484 AC: 20041 AN: 41446

American (AMR) AF: 0.508 AC: 7753 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1797 AN: 5152

South Asian (SAS) AF: 0.569 AC: 2745 AN: 4826

European-Finnish (FIN) AF: 0.526 AC: 5563 AN: 10584

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

European-Non Finnish (NFE) AF: 0.522 AC: 35477 AN: 67934

Other (OTH) AF: 0.523 AC: 1103 AN: 2110

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
PhyloP100		-0.67
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: rs3004070; hg19: chr6-39869952; COSMIC: COSV51321162; COSMIC: COSV51321162;