chr22-41572129-G-A

Variant names:

• chr22-41572129-G-A
• rs762132125
• NM_014460.4:c.164G>A

Variant summary

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

The NM_014460.4(CSDC2):​c.164G>A​(p.Arg55Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000085 in 1,176,974 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R55T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: CSDC2 NM_014460.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

CSDC2 (HGNC:30359): (cold shock domain containing C2) Predicted to enable mRNA 3'-UTR binding activity. Predicted to be involved in regulation of mRNA stability. Predicted to be located in nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014460.4. 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
	CSDC2	NM_014460.4	MANE Select	c.164G>A	p.Arg55Lys	missense	Exon 2 of 4	NP_055275.1	Q9Y534

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSDC2	ENST00000306149.12	TSL:1 MANE Select	c.164G>A	p.Arg55Lys	missense	Exon 2 of 4	ENSP00000302485.7	Q9Y534
	CSDC2	ENST00000901851.1		c.164G>A	p.Arg55Lys	missense	Exon 3 of 5	ENSP00000571910.1
	CSDC2	ENST00000901852.1		c.164G>A	p.Arg55Lys	missense	Exon 2 of 4	ENSP00000571911.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.50e-7 AC: 1 AN: 1176974 Hom.: 0 Cov.: 32 AF XY: 0.00000177 AC XY: 1 AN XY: 564628

African (AFR) AF: 0.00 AC: 0 AN: 25000

American (AMR) AF: 0.00 AC: 0 AN: 14010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15446

East Asian (EAS) AF: 0.00 AC: 0 AN: 29934

South Asian (SAS) AF: 0.00 AC: 0 AN: 33002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4684

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 965474

Other (OTH) AF: 0.00 AC: 0 AN: 47288

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.060	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		10
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.019	D
Polyphen		0.97	D
Vest4		0.68
MutPred		0.34		Gain of solvent accessibility (P = 0.0022)
MVP		0.67
MPC		1.4
ClinPred		0.99	D
GERP RS		5.0
PromoterAI		0.012	Neutral
Varity_R		0.84
gMVP		0.60
Mutation Taster		=27/73	disease causing

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: rs762132125; hg19: chr22-41968133;