rs6919807

Variant names:

• chr6-39864488-G-A
• rs6919807
• NM_001201427.2:c.314G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-39864488-G-A
• chr6-39864488-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001201427.2(DAAM2):​c.314G>A​(p.Arg105His) variant causes a missense change. The variant allele was found at a frequency of 0.00118 in 1,611,824 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R105C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0046 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00082 (7 hom.)
• Consequence: DAAM2 NM_001201427.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.29
• Publications: 9 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]

DAAM2-AS1 (HGNC:40830): (DAAM2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0097029805).
• BP6: Variant 6-39864488-G-A is Benign according to our data. Variant chr6-39864488-G-A is described in ClinVar as Benign. ClinVar VariationId is 3039055.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000819 (1195/1459632) while in subpopulation AFR AF = 0.0168 (563/33424). AF 95% confidence interval is 0.0157. There are 7 homozygotes in GnomAdExome4. There are 569 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201427.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	NM_001201427.2	MANE Select	c.314G>A	p.Arg105His	missense	Exon 4 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.314G>A	p.Arg105His	missense	Exon 4 of 25	NP_056160.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAAM2	ENST00000274867.9	TSL:1 MANE Select	c.314G>A	p.Arg105His	missense	Exon 4 of 25	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.314G>A	p.Arg105His	missense	Exon 4 of 25	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000491083.2	TSL:1	n.460G>A		non_coding_transcript_exon	Exon 4 of 14

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152074 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00172 AC: 425 AN: 246724 AF XY: 0.00135

Gnomad AFR exome AF: 0.0150

Gnomad AMR exome AF: 0.00178

Gnomad ASJ exome AF: 0.0100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000241

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.000819 AC: 1195 AN: 1459632 Hom.: 7 Cov.: 31 AF XY: 0.000784 AC XY: 569 AN XY: 725962

African (AFR) AF: 0.0168 AC: 563 AN: 33424

American (AMR) AF: 0.00188 AC: 84 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00931 AC: 243 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.0000582 AC: 5 AN: 85852

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53322

Middle Eastern (MID) AF: 0.00241 AC: 12 AN: 4982

European-Non Finnish (NFE) AF: 0.000155 AC: 172 AN: 1111432

Other (OTH) AF: 0.00191 AC: 115 AN: 60242

GnomAD4 genome AF: 0.00462 AC: 703 AN: 152192 Hom.: 5 Cov.: 32 AF XY: 0.00430 AC XY: 320 AN XY: 74408

African (AFR) AF: 0.0146 AC: 608 AN: 41522

American (AMR) AF: 0.00255 AC: 39 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68010

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00217 Hom.: 5

Bravo AF: 0.00524

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0125 AC: 50

ESP6500EA AF: 0.000838 AC: 7

ExAC AF: 0.00169 AC: 205

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000238

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DAAM2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0097	T
MetaSVM	Uncertain	0.53	D
MutationAssessor	Benign	1.8	L
PhyloP100		4.3
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.52
MVP		0.74
MPC		0.72
ClinPred		0.034	T
GERP RS		5.9
Varity_R		0.35
gMVP		0.61
Mutation Taster		=96/4	polymorphism

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: rs6919807; hg19: chr6-39832264; COSMIC: COSV99224783; COSMIC: COSV99224783;