6-39900192-A-G

Position:

• chr6-39900192-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001201427.2(DAAM2):​c.2795A>G​(p.Asn932Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,610,068 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (24 hom.)
• Consequence: DAAM2 NM_001201427.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.183

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]

DAAM2 (HGNC:):

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056210756).
• BP6: Variant 6-39900192-A-G is Benign according to our data. Variant chr6-39900192-A-G is described in ClinVar as [Benign]. Clinvar id is 3044549.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAAM2	NM_001201427.2	c.2795A>G	p.Asn932Ser	missense_variant	23/25	ENST00000274867.9	NP_001188356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAAM2	ENST00000274867.9	c.2795A>G	p.Asn932Ser	missense_variant	23/25	1	NM_001201427.2	ENSP00000274867.4

Frequencies

GnomAD3 genomes AF: 0.000736 AC: 112 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00893

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00221 AC: 536 AN: 242004 Hom.: 8 AF XY: 0.00289 AC XY: 379 AN XY: 131188

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00138

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0141

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000648

Gnomad OTH exome AF: 0.000675

GnomAD4 exome AF: 0.00116 AC: 1688 AN: 1457810 Hom.: 24 Cov.: 30 AF XY: 0.00158 AC XY: 1148 AN XY: 724788

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00133

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000265

Gnomad4 OTH exome AF: 0.00126

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000833 AC XY: 62 AN XY: 74438

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00873

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000380 Hom.: 0

Bravo AF: 0.000763

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000249 AC: 1

ESP6500EA AF: 0.000482 AC: 4

ExAC AF: 0.00218 AC: 264

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DAAM2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.77
DEOGEN2	Benign	0.022	T;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.77	T;.;T;T
MetaRNN	Benign	0.0056	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.085	.;N;.;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.60	.;N;N;N
REVEL	Benign	0.057
Sift	Benign	0.73	.;T;T;T
Sift4G	Benign	0.85	T;T;T;T
Polyphen		0.024	.;B;.;B
Vest4		0.16
MVP		0.39
MPC		0.12
ClinPred		0.0095	T
GERP RS		-2.1
Varity_R		0.043
gMVP		0.094

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: rs201309255; hg19: chr6-39867968;