19-13906456-AGGACCCCCG-AGGACCCCCGGGACCCCCG

Variant names:

• chr19-13906456-A-AGGACCCCCG
• rs1028125077
• NM_017721.5:c.27_35dupACCCCCGGG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_017721.5(CC2D1A):​c.27_35dupACCCCCGGG​(p.Gly12_Arg13insProProGly) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000132 in 1,365,402 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: CC2D1A NM_017721.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• Publications: 0 publications found

Genes affected

CC2D1A (HGNC:30237): (coiled-coil and C2 domain containing 1A) This gene encodes a transcriptional repressor that binds to a conserved 14-bp 5'-repressor element and regulates expression of the 5-hydroxytryptamine (serotonin) receptor 1A gene in neuronal cells. The DNA binding and transcriptional repressor activities of the protein are inhibited by calcium. A mutation in this gene results in a nonsyndromic form of cognitive disability (MRT3). [provided by RefSeq, Jul 2017]

BRME1 (HGNC:28153): (break repair meiotic recombinase recruitment factor 1) Predicted to be involved in meiosis I and spermatogenesis. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_017721.5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017721.5. 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
	CC2D1A	NM_017721.5	MANE Select	c.27_35dupACCCCCGGG	p.Gly12_Arg13insProProGly	disruptive_inframe_insertion	Exon 1 of 29	NP_060191.3
	CC2D1A	NM_001411138.1		c.27_35dupACCCCCGGG	p.Gly12_Arg13insProProGly	disruptive_inframe_insertion	Exon 1 of 29	NP_001398067.1	Q6P1N0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D1A	ENST00000318003.11	TSL:1 MANE Select	c.27_35dupACCCCCGGG	p.Gly12_Arg13insProProGly	disruptive_inframe_insertion	Exon 1 of 29	ENSP00000313601.6	Q6P1N0-1
	CC2D1A	ENST00000589606.5	TSL:1	c.27_35dupACCCCCGGG	p.Gly12_Arg13insProProGly	disruptive_inframe_insertion	Exon 1 of 29	ENSP00000467526.1	Q6P1N0-2
	CC2D1A	ENST00000870936.1		c.27_35dupACCCCCGGG	p.Gly12_Arg13insProProGly	disruptive_inframe_insertion	Exon 1 of 28	ENSP00000540995.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000132 AC: 18 AN: 1365402 Hom.: 0 Cov.: 30 AF XY: 0.0000104 AC XY: 7 AN XY: 673358

African (AFR) AF: 0.00 AC: 0 AN: 29080

American (AMR) AF: 0.00 AC: 0 AN: 32784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24324

East Asian (EAS) AF: 0.00 AC: 0 AN: 31960

South Asian (SAS) AF: 0.00 AC: 0 AN: 76768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5254

European-Non Finnish (NFE) AF: 0.0000169 AC: 18 AN: 1066906

Other (OTH) AF: 0.00 AC: 0 AN: 56704

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3
Mutation Taster		=79/21	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1028125077; hg19: chr19-14017269;