12-4273992-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001759.4(CCND2):c.-49T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,571,080 control chromosomes in the GnomAD database, including 778,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.97 ( 72379 hom., cov: 31)

Exomes 𝑓: 1.0 ( 706152 hom. )

Consequence

CCND2
NM_001759.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0480

Variant links:

Genes affected

CCND2 (HGNC:1583): (cyclin D2) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with CDK4 or CDK6 and functions as a regulatory subunit of the complex, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular tumors. Mutations in this gene are associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (MPPH3). [provided by RefSeq, Sep 2014]

CCND2 links:

CCND2-AS1 (HGNC:49398): (CCND2 antisense RNA 1)

CCND2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-4273992-T-C is Benign according to our data. Variant chr12-4273992-T-C is described in ClinVar as [Benign]. Clinvar id is 1192627.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
CCND2	NM_001759.4 linkuse as main transcript	c.-49T>C	5_prime_UTR_variant	1/5	ENST00000261254.8
CCND2-AS1	NR_125790.1 linkuse as main transcript	n.126+2067A>G	intron_variant, non_coding_transcript_variant
CCND2-AS1	NR_149145.1 linkuse as main transcript	n.182+1304A>G	intron_variant, non_coding_transcript_variant
CCND2-AS1	NR_149146.1 linkuse as main transcript	n.182+1304A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND2	ENST00000261254.8 linkuse as main transcript	c.-49T>C		5_prime_UTR_variant	1/5	1	NM_001759.4	P1	P30279-1
CCND2-AS1	ENST00000663068.1 linkuse as main transcript	n.194+2067A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.974

AC:

148201

AN:

152100

Hom.:

72318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.911

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.990

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.980

GnomAD3 exomes

AF:

0.994

AC:

200560

AN:

201822

Hom.:

99691

AF XY:

0.995

AC XY:

109764

AN XY:

110286

show subpopulations

Gnomad AFR exome

AF:

0.907

Gnomad AMR exome

AF:

0.995

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.998

AC:

1415437

AN:

1418862

Hom.:

706152

Cov.:

AF XY:

0.998

AC XY:

701687

AN XY:

703146

show subpopulations

Gnomad4 AFR exome

AF:

0.912

Gnomad4 AMR exome

AF:

0.995

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.974

AC:

148322

AN:

152218

Hom.:

72379

Cov.:

AF XY:

0.975

AC XY:

72582

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.911

Gnomad4 AMR

AF:

0.990

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.981

Alfa

AF:

0.994

Hom.:

26620

Bravo

AF:

0.971

Asia WGS

AF:

0.997

AC:

3467

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

6.3

Dann

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over