16-30006255-TGC-AGT

Variant names:

• chr16-30006255-TGC-AGT
• NM_003586.3:c.1132_1134delGCAinsACT
• DOC2A p.Ala378Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003586.3(DOC2A):​c.1132_1134delGCAinsACT​(p.Ala378Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DOC2A NM_003586.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 0 publications found

Genes affected

DOC2A (HGNC:2985): (double C2 domain alpha) There are at least two protein isoforms of the Double C2 protein, namely alpha (DOC2A) and beta (DOC2B), which contain two C2-like domains. DOC2A and DOC2B are encoded by different genes; these genes are at times confused with the unrelated DAB2 gene which was initially named DOC-2. DOC2A is mainly expressed in brain and is suggested to be involved in Ca(2+)-dependent neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003586.3. 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
	DOC2A	NM_003586.3	MANE Select	c.1132_1134delGCAinsACT	p.Ala378Thr	missense	N/A	NP_003577.2
	DOC2A	NM_001282062.1		c.1132_1134delGCAinsACT	p.Ala378Thr	missense	N/A	NP_001268991.1	Q14183-1
	DOC2A	NM_001282063.2		c.1132_1134delGCAinsACT	p.Ala378Thr	missense	N/A	NP_001268992.1	Q14183-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOC2A	ENST00000350119.9	TSL:1 MANE Select	c.1132_1134delGCAinsACT	p.Ala378Thr	missense	N/A	ENSP00000340017.4	Q14183-1
	DOC2A	ENST00000564979.5	TSL:1	c.1132_1134delGCAinsACT	p.Ala378Thr	missense	N/A	ENSP00000455624.1	Q14183-1
	DOC2A	ENST00000616445.4	TSL:1	c.1132_1134delGCAinsACT	p.Ala378Thr	missense	N/A	ENSP00000482870.1	Q14183-1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.58

Splicing

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

hg19: chr16-30017576;