rs2972388

Variant names:

• chr5-69235426-C-A
• rs2972388
• NM_001799.4:c.99C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-69235426-C-A
• chr5-69235426-C-G
• chr5-69235426-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001799.4(CDK7):​c.99C>A​(p.Asn33Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,447,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: CDK7 NM_001799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.526
• Publications: 36 publications found

Genes affected

CDK7 (HGNC:1778): (cyclin dependent kinase 7) The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This protein forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK). It is an essential component of the transcription factor TFIIH, that is involved in transcription initiation and DNA repair. This protein is thought to serve as a direct link between the regulation of transcription and the cell cycle. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10846636).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001799.4. 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
	CDK7	NM_001799.4	MANE Select	c.99C>A	p.Asn33Lys	missense	Exon 2 of 12	NP_001790.1	A0A0S2Z3F9
	CDK7	NM_001324070.2		c.99C>A	p.Asn33Lys	missense	Exon 2 of 9	NP_001310999.1
	CDK7	NM_001324071.2		c.65C>A	p.Thr22Lys	missense	Exon 2 of 10	NP_001311000.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK7	ENST00000256443.8	TSL:1 MANE Select	c.99C>A	p.Asn33Lys	missense	Exon 2 of 12	ENSP00000256443.3	P50613
	CDK7	ENST00000512687.5	TSL:1	n.214C>A		non_coding_transcript_exon	Exon 2 of 5
	CDK7	ENST00000890327.1		c.99C>A	p.Asn33Lys	missense	Exon 2 of 12	ENSP00000560386.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250598 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1447828 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 721186

African (AFR) AF: 0.00 AC: 0 AN: 33060

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 85842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099510

Other (OTH) AF: 0.0000501 AC: 3 AN: 59880

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 17135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.53
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.15	N
REVEL	Benign	0.078
Sift	Benign	0.88	T
Sift4G	Benign	0.84	T
Polyphen		0.0	B
Vest4		0.45
MutPred		0.37		Gain of methylation at N33 (P = 0.0342)
MVP		0.62
MPC		0.75
ClinPred		0.24	T
GERP RS		4.0
PromoterAI		-0.037	Neutral
Varity_R		0.22
gMVP		0.27
Mutation Taster		=77/23	polymorphism

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: rs2972388; hg19: chr5-68531253;