rs882559

chr6-39901290-G-Cchr6-39901290-G-T

Variant summary

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

The NM_001201427.2(DAAM2):c.2812-12G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,609,308 control chromosomes in the GnomAD database, including 251,444 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 0.59 (27107 hom., cov: 32)
  • Exomes 𝑓: 0.55 (224337 hom.)
• Consequence: DAAM2 NM_001201427.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003844
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAAM2	NM_001201427.2	c.2812-12G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000274867.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAAM2	ENST00000274867.9	c.2812-12G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001201427.2	P1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90171 AN: 151926 Hom.: 27077 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.607

GnomAD3 exomes AF: 0.575 AC: 141725 AN: 246390 Hom.: 41170 AF XY: 0.575 AC XY: 76826 AN XY: 133590

Gnomad AFR exome AF: 0.697

Gnomad AMR exome AF: 0.577

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.607

Gnomad SAS exome AF: 0.622

Gnomad FIN exome AF: 0.531

Gnomad NFE exome AF: 0.549

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.553 AC: 806256 AN: 1457264 Hom.: 224337 Cov.: 36 AF XY: 0.555 AC XY: 402455 AN XY: 724838

Gnomad4 AFR exome AF: 0.701

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.594 AC: 90244 AN: 152044 Hom.: 27107 Cov.: 32 AF XY: 0.593 AC XY: 44106 AN XY: 74316

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.606

Alfa AF: 0.488 Hom.: 2544

Bravo AF: 0.603

Asia WGS AF: 0.581 AC: 2025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.7
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.0
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: rs882559; hg19: chr6-39869066; COSMIC: COSV51354722; COSMIC: COSV51354722;