19-10567956-T-C

Variant names:

• chr19-10567956-T-C
• rs1465702
• NM_001800.4:c.142-539A>G

Variant summary

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

The NM_001800.4(CDKN2D):​c.142-539A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 152,120 control chromosomes in the GnomAD database, including 70,340 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 0.96 (70340 hom., cov: 29)
• Consequence: CDKN2D NM_001800.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09
• Publications: 3 publications found

Genes affected

CDKN2D (HGNC:1790): (cyclin dependent kinase inhibitor 2D) The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to form a stable complex with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. The abundance of the transcript of this gene was found to oscillate in a cell-cycle dependent manner with the lowest expression at mid G1 and a maximal expression during S phase. The negative regulation of the cell cycle involved in this protein was shown to participate in repressing neuronal proliferation, as well as spermatogenesis. Two alternatively spliced variants of this gene, which encode an identical protein, have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN2D	NM_001800.4	c.142-539A>G		intron_variant	Intron 1 of 1	ENST00000393599.3	NP_001791.1
CDKN2D	NM_079421.3	c.142-539A>G		intron_variant	Intron 2 of 2		NP_524145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN2D	ENST00000393599.3	c.142-539A>G		intron_variant	Intron 1 of 1	1	NM_001800.4	ENSP00000377224.1
CDKN2D	ENST00000335766.2	c.142-539A>G		intron_variant	Intron 2 of 2	1		ENSP00000337056.1

Frequencies

GnomAD3 genomes AF: 0.961 AC: 146131 AN: 152002 Hom.: 70287 Cov.: 29

Gnomad AFR AF: 0.990

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.961 AC: 146244 AN: 152120 Hom.: 70340 Cov.: 29 AF XY: 0.960 AC XY: 71397 AN XY: 74362

African (AFR) AF: 0.990 AC: 41059 AN: 41476

American (AMR) AF: 0.958 AC: 14611 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3125 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5157 AN: 5162

South Asian (SAS) AF: 0.939 AC: 4527 AN: 4820

European-Finnish (FIN) AF: 0.931 AC: 9874 AN: 10604

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.951 AC: 64699 AN: 68008

Other (OTH) AF: 0.957 AC: 2023 AN: 2114

Alfa AF: 0.950 Hom.: 13917

Bravo AF: 0.965

Asia WGS AF: 0.970 AC: 3373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.70
DANN	Benign	0.41
PhyloP100		-3.1
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: rs1465702; hg19: chr19-10678632;