12-6528950-C-G

Variant names:

• chr12-6528950-C-G
• rs740850
• NM_014865.4:c.3483C>G

Variant summary

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

The NM_014865.4(NCAPD2):​c.3483C>G​(p.Asn1161Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N1161N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCAPD2 NM_014865.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 29 publications found

Genes affected

NCAPD2 (HGNC:24305): (non-SMC condensin I complex subunit D2) Enables histone binding activity. Involved in mitotic chromosome condensation. Located in condensed chromosome; cytosol; and nucleoplasm. Part of condensin complex. Colocalizes with cytoplasm and nuclear chromosome. Implicated in primary autosomal recessive microcephaly. [provided by Alliance of Genome Resources, Apr 2022]

GAPDH-DT (HGNC:55492): (GAPDH divergent transcript)

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_014865.4. 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
	NCAPD2	NM_014865.4	MANE Select	c.3483C>G	p.Asn1161Lys	missense	Exon 27 of 32	NP_055680.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAPD2	ENST00000315579.10	TSL:1 MANE Select	c.3483C>G	p.Asn1161Lys	missense	Exon 27 of 32	ENSP00000325017.5	Q15021
	NCAPD2	ENST00000925386.1		c.3606C>G	p.Asn1202Lys	missense	Exon 28 of 33	ENSP00000595445.1
	NCAPD2	ENST00000925390.1		c.3522C>G	p.Asn1174Lys	missense	Exon 27 of 32	ENSP00000595449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 6403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-1.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.59		Gain of catalytic residue at I1163 (P = 0.0031)
MVP		0.30
MPC		0.80
ClinPred		1.0	D
GERP RS		-4.3
Varity_R		0.95
gMVP		0.67
Mutation Taster		=34/66	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: rs740850; hg19: chr12-6638116;