rs1049606

Variant names:

• chr12-4273870-C-A
• rs1049606
• ENST00000674624.1:n.-171C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000674624.1(ENSG00000285901):​n.-171C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
• Consequence: ENSG00000285901 ENST00000674624.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 19 publications found

Genes affected

ENSG00000285901 (HGNC:):

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

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=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND2	NM_001759.4	c.-171C>A		5_prime_UTR_variant	Exon 1 of 5	ENST00000261254.8	NP_001750.1
CCND2-AS1	NR_125790.1	n.126+2189G>T		intron_variant	Intron 1 of 1
CCND2-AS1	NR_149145.1	n.182+1426G>T		intron_variant	Intron 1 of 3
CCND2-AS1	NR_149146.1	n.182+1426G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285901	ENST00000674624.1	n.-171C>A		non_coding_transcript_exon_variant	Exon 1 of 10			ENSP00000501898.1
CCND2	ENST00000261254.8	c.-171C>A		5_prime_UTR_variant	Exon 1 of 5	1	NM_001759.4	ENSP00000261254.3
ENSG00000285901	ENST00000674624.1	n.-171C>A		5_prime_UTR_variant	Exon 1 of 10			ENSP00000501898.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.8
DANN	Benign	0.57
PhyloP100		1.9
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;