Genetic Variant NM_017721.5:c.37A>C (chr19-13906478-A-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_017721.5(CC2D1A):c.37A>C(p.Arg13Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000515 in 1,359,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

CC2D1A
NM_017721.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.47

Publications

0 publications found

Variant links:

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 links:

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]

BRME1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 19-13906478-A-C is Benign according to our data. Variant chr19-13906478-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3713252.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.47 with no splicing effect.

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.37A>C	p.Arg13Arg	synonymous	Exon 1 of 29	NP_060191.3
	CC2D1A	NM_001411138.1		c.37A>C	p.Arg13Arg	synonymous	Exon 1 of 29	NP_001398067.1	Q6P1N0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CC2D1A	ENST00000318003.11	TSL:1 MANE Select	c.37A>C	p.Arg13Arg	synonymous	Exon 1 of 29	ENSP00000313601.6	Q6P1N0-1
CC2D1A	ENST00000589606.5	TSL:1	c.37A>C	p.Arg13Arg	synonymous	Exon 1 of 29	ENSP00000467526.1	Q6P1N0-2
CC2D1A	ENST00000870936.1		c.37A>C	p.Arg13Arg	synonymous	Exon 1 of 28	ENSP00000540995.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000942

AC:

AN:

106172

AF XY:

0.0000168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000515

AC:

AN:

1359956

Hom.:

Cov.:

AF XY:

0.00000596

AC XY:

AN XY:

670694

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28906

American (AMR)

AF:

0.00

AC:

AN:

32250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24212

East Asian (EAS)

AF:

0.00

AC:

AN:

31846

South Asian (SAS)

AF:

0.0000131

AC:

AN:

76602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39864

Middle Eastern (MID)

AF:

0.000395

AC:

AN:

5064

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1064648

Other (OTH)

AF:

0.0000354

AC:

AN:

56564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.50

PhyloP100

1.5

PromoterAI

0.076

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over