1-32209314-G-A

Variant names:

• chr1-32209314-G-A
• rs200429239
• NM_001099434.2:c.221G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099434.2(DCDC2B):​c.221G>A​(p.Arg74Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R74I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: DCDC2B NM_001099434.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.69
• Publications: 0 publications found

Genes affected

DCDC2B (HGNC:32576): (doublecortin domain containing 2B) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two doublecortin domains. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. [provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1822977).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099434.2. 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
	DCDC2B	NM_001099434.2	MANE Select	c.221G>A	p.Arg74Lys	missense	Exon 1 of 9	NP_001092904.1	A2VCK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2B	ENST00000409358.2	TSL:1 MANE Select	c.221G>A	p.Arg74Lys	missense	Exon 1 of 9	ENSP00000386870.1	A2VCK2
	DCDC2B	ENST00000906474.1		c.221G>A	p.Arg74Lys	missense	Exon 1 of 9	ENSP00000576533.1
	DCDC2B	ENST00000487056.1	TSL:2	n.219G>A		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249226 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461702 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10 AN XY: 727134

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111866

Other (OTH) AF: 0.0000166 AC: 1 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
PhyloP100		7.7
PromoterAI		0.051	Neutral
Varity_R		0.26
gMVP		0.38
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs200429239; hg19: chr1-32674915;