16-30006685-TG-T

Variant names:

• chr16-30006685-TG-T
• rs532922507
• NM_003586.3:c.879-9delC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_003586.3(DOC2A):​c.879-9delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,611,892 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0029 (4 hom.)
• Consequence: DOC2A NM_003586.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.699

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 16-30006685-TG-T is Benign according to our data. Variant chr16-30006685-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 787686.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOC2A	NM_003586.3	c.879-9delC		intron_variant	Intron 8 of 10	ENST00000350119.9	NP_003577.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOC2A	ENST00000350119.9	c.879-9delC		intron_variant	Intron 8 of 10	1	NM_003586.3	ENSP00000340017.4

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 257 AN: 149932 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000839

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000776

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00315

Gnomad OTH AF: 0.000487

GnomAD3 exomes AF: 0.00134 AC: 337 AN: 251422 Hom.: 0 AF XY: 0.00135 AC XY: 183 AN XY: 135908

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00256

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00288 AC: 4207 AN: 1461840 Hom.: 4 Cov.: 39 AF XY: 0.00278 AC XY: 2025 AN XY: 727238

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00105

Gnomad4 NFE exome AF: 0.00363

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00171 AC: 257 AN: 150052 Hom.: 0 Cov.: 31 AF XY: 0.00143 AC XY: 105 AN XY: 73216

Gnomad4 AFR AF: 0.000837

Gnomad4 AMR AF: 0.0000664

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000776

Gnomad4 NFE AF: 0.00315

Gnomad4 OTH AF: 0.000481

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.00155

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs532922507; hg19: chr16-30018006;