rs1049606

Variant names:

• chr12-4273870-C-T
• rs1049606
• NM_001759.4:c.-171C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-4273870-C-T
• chr12-4273870-C-A
• chr12-4273870-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001759.4(CCND2):​c.-171C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 661,906 control chromosomes in the GnomAD database, including 112,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (25784 hom., cov: 31)
  • Exomes 𝑓: 0.58 (86416 hom.)
• Consequence: CCND2 NM_001759.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.88
• Publications: 19 publications found

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]

ENSG00000285901 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-4273870-C-T is Benign according to our data. Variant chr12-4273870-C-T is described in ClinVar as Benign. ClinVar VariationId is 678294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001759.4. 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
	CCND2	NM_001759.4	MANE Select	c.-171C>T		5_prime_UTR	Exon 1 of 5	NP_001750.1	P30279-1
	CCND2-AS1	NR_125790.1		n.126+2189G>A		intron	N/A
	CCND2-AS1	NR_149145.1		n.182+1426G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND2	ENST00000261254.8	TSL:1 MANE Select	c.-171C>T		5_prime_UTR	Exon 1 of 5	ENSP00000261254.3	P30279-1
	ENSG00000285901	ENST00000674624.1		n.-171C>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000501898.1	A0A6Q8PFP0
	ENSG00000285901	ENST00000674624.1		n.-171C>T		5_prime_UTR	Exon 1 of 10	ENSP00000501898.1	A0A6Q8PFP0

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88116 AN: 151860 Hom.: 25742 Cov.: 31

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.579 AC: 295474 AN: 509928 Hom.: 86416 Cov.: 6 AF XY: 0.575 AC XY: 153040 AN XY: 266150

African (AFR) AF: 0.555 AC: 7428 AN: 13394

American (AMR) AF: 0.686 AC: 12792 AN: 18654

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 8830 AN: 13984

East Asian (EAS) AF: 0.633 AC: 19742 AN: 31180

South Asian (SAS) AF: 0.481 AC: 22831 AN: 47452

European-Finnish (FIN) AF: 0.541 AC: 16289 AN: 30088

Middle Eastern (MID) AF: 0.609 AC: 1276 AN: 2094

European-Non Finnish (NFE) AF: 0.583 AC: 189541 AN: 325014

Other (OTH) AF: 0.597 AC: 16745 AN: 28068

GnomAD4 genome AF: 0.580 AC: 88219 AN: 151978 Hom.: 25784 Cov.: 31 AF XY: 0.581 AC XY: 43193 AN XY: 74324

African (AFR) AF: 0.557 AC: 23087 AN: 41428

American (AMR) AF: 0.667 AC: 10194 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2167 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3642 AN: 5150

South Asian (SAS) AF: 0.461 AC: 2217 AN: 4806

European-Finnish (FIN) AF: 0.544 AC: 5751 AN: 10578

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39061 AN: 67948

Other (OTH) AF: 0.603 AC: 1273 AN: 2112

Alfa AF: 0.594 Hom.: 29595

Bravo AF: 0.599

Asia WGS AF: 0.617 AC: 2147 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.58
PhyloP100		1.9
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs1049606; hg19: chr12-4383036; COSMIC: COSV54222306; COSMIC: COSV54222306;