19-13906511-C-G

Variant names:

• chr19-13906511-C-G
• rs769120532
• NM_017721.5:c.60+10C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017721.5(CC2D1A):​c.60+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,325,654 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CC2D1A NM_017721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5	c.60+10C>G		intron_variant	Intron 1 of 28	ENST00000318003.11	NP_060191.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D1A	ENST00000318003.11	c.60+10C>G		intron_variant	Intron 1 of 28	1	NM_017721.5	ENSP00000313601.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000226 AC: 3 AN: 1325654 Hom.: 0 Cov.: 30 AF XY: 0.00000153 AC XY: 1 AN XY: 652712

African (AFR) AF: 0.00 AC: 0 AN: 27130

American (AMR) AF: 0.00 AC: 0 AN: 27404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23116

East Asian (EAS) AF: 0.00 AC: 0 AN: 29242

South Asian (SAS) AF: 0.00 AC: 0 AN: 73124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4746

European-Non Finnish (NFE) AF: 0.00000286 AC: 3 AN: 1049676

Other (OTH) AF: 0.00 AC: 0 AN: 55070

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		-0.36
PromoterAI		0.062	Neutral

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: rs769120532; hg19: chr19-14017324;