chr19-10567956-T-C

Position:

• chr19-10567956-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CDKN2D	NM_001800.4	c.142-539A>G		intron_variant		ENST00000393599.3	NP_001791.1
CDKN2D	NM_079421.3	c.142-539A>G		intron_variant			NP_524145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2D	ENST00000393599.3	c.142-539A>G		intron_variant		1	NM_001800.4	ENSP00000377224	P1
CDKN2D	ENST00000335766.2	c.142-539A>G		intron_variant		1		ENSP00000337056	P1

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

Gnomad4 AFR AF: 0.990

Gnomad4 AMR AF: 0.958

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.939

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.951

Gnomad4 OTH AF: 0.957

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

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

Other links and lift over

dbSNP: rs1465702; hg19: chr19-10678632;