rs6511901

Variant names:

• chr19-13916839-C-T
• rs6511901
• NM_017721.5:c.749-1231C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017721.5(CC2D1A):​c.749-1231C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,964 control chromosomes in the GnomAD database, including 16,107 homozygotes. 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: 𝑓 0.38 (16107 hom., cov: 32)
• Consequence: CC2D1A NM_017721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 5 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]

CC2D1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal recessive 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5	c.749-1231C>T		intron_variant	Intron 6 of 28	ENST00000318003.11	NP_060191.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D1A	ENST00000318003.11	c.749-1231C>T		intron_variant	Intron 6 of 28	1	NM_017721.5	ENSP00000313601.6
CC2D1A	ENST00000589606.5	c.749-1231C>T		intron_variant	Intron 6 of 28	1		ENSP00000467526.1
CC2D1A	ENST00000586955.5	n.284-1231C>T		intron_variant	Intron 2 of 23	1		ENSP00000465376.1
CC2D1A	ENST00000585896.5	n.806-1231C>T		intron_variant	Intron 4 of 9	2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58031 AN: 151846 Hom.: 16048 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.383 AC: 58155 AN: 151964 Hom.: 16107 Cov.: 32 AF XY: 0.378 AC XY: 28065 AN XY: 74290

African (AFR) AF: 0.785 AC: 32552 AN: 41448

American (AMR) AF: 0.367 AC: 5595 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3468

East Asian (EAS) AF: 0.308 AC: 1597 AN: 5178

South Asian (SAS) AF: 0.281 AC: 1356 AN: 4824

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10572

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14003 AN: 67932

Other (OTH) AF: 0.337 AC: 706 AN: 2096

Alfa AF: 0.264 Hom.: 3829

Bravo AF: 0.416

Asia WGS AF: 0.373 AC: 1293 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.87
DANN	Benign	0.41
PhyloP100		-0.043
Mutation Taster		=100/0	polymorphism (auto)

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: rs6511901; hg19: chr19-14027652;