6-39856329-T-C

Variant names:

• chr6-39856329-T-C
• rs11965120
• NM_001201427.2:c.27T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001201427.2(DAAM2):​c.27T>C​(p.His9His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,548,998 control chromosomes in the GnomAD database, including 288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 32)
  • Exomes 𝑓: 0.014 (268 hom.)
• Consequence: DAAM2 NM_001201427.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.61
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-39856329-T-C is Benign according to our data. Variant chr6-39856329-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060337.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

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.27T>C	p.His9His	synonymous	Exon 2 of 25	NP_001188356.1	Q86T65-3
	DAAM2	NM_015345.4		c.27T>C	p.His9His	synonymous	Exon 2 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.27T>C	p.His9His	synonymous	Exon 2 of 25	ENSP00000274867.4	Q86T65-3
	DAAM2	ENST00000538976.5	TSL:1	c.27T>C	p.His9His	synonymous	Exon 2 of 25	ENSP00000437808.1	Q86T65-4
	DAAM2	ENST00000405961.3	TSL:1	c.27T>C	p.His9His	synonymous	Exon 2 of 3	ENSP00000384637.3	F2Z2Q2

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1859 AN: 152204 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0135 AC: 2240 AN: 165822 AF XY: 0.0138

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00854

Gnomad EAS exome AF: 0.0569

Gnomad FIN exome AF: 0.00454

Gnomad NFE exome AF: 0.0139

Gnomad OTH exome AF: 0.0136

GnomAD4 exome AF: 0.0142 AC: 19792 AN: 1396676 Hom.: 268 Cov.: 31 AF XY: 0.0140 AC XY: 9690 AN XY: 690098

African (AFR) AF: 0.00566 AC: 176 AN: 31100

American (AMR) AF: 0.00989 AC: 357 AN: 36108

Ashkenazi Jewish (ASJ) AF: 0.00772 AC: 187 AN: 24214

East Asian (EAS) AF: 0.0756 AC: 2639 AN: 34898

South Asian (SAS) AF: 0.00695 AC: 532 AN: 76564

European-Finnish (FIN) AF: 0.00530 AC: 268 AN: 50610

Middle Eastern (MID) AF: 0.0432 AC: 241 AN: 5580

European-Non Finnish (NFE) AF: 0.0135 AC: 14549 AN: 1079664

Other (OTH) AF: 0.0146 AC: 843 AN: 57938

GnomAD4 genome AF: 0.0122 AC: 1859 AN: 152322 Hom.: 20 Cov.: 32 AF XY: 0.0118 AC XY: 880 AN XY: 74494

African (AFR) AF: 0.00539 AC: 224 AN: 41578

American (AMR) AF: 0.0146 AC: 224 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.0591 AC: 306 AN: 5180

South Asian (SAS) AF: 0.00973 AC: 47 AN: 4828

European-Finnish (FIN) AF: 0.00452 AC: 48 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 944 AN: 68020

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.00999 Hom.: 11

Bravo AF: 0.0124

Asia WGS AF: 0.0270 AC: 95 AN: 3478

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
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.5
DANN	Benign	0.62
PhyloP100		2.6
Mutation Taster		=100/0	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: rs11965120; hg19: chr6-39824105; COSMIC: COSV51302213;