NCAPD2 p.His1096Leu

Variant names:

• chr12-6528316-A-T
• NM_014865.4:c.3287A>T
• NCAPD2 p.His1096Leu

Your query was ambiguous. Multiple possible variants found:

• chr12-6528316-A-T
• chr12-6528316-AT-TC
• chr12-6528316-AT-TA
• chr12-6528316-AT-TG
• chr12-6528315-CAT-TTA
• chr12-6528315-CAT-TTG

Variant summary

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

The NM_014865.4(NCAPD2):​c.3287A>T​(p.His1096Leu) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1096Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCAPD2 NM_014865.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95
• Publications: 0 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.3287A>T	p.His1096Leu	missense	Exon 25 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.3287A>T	p.His1096Leu	missense	Exon 25 of 32	ENSP00000325017.5	Q15021
	NCAPD2	ENST00000925386.1		c.3410A>T	p.His1137Leu	missense	Exon 26 of 33	ENSP00000595445.1
	NCAPD2	ENST00000925390.1		c.3326A>T	p.His1109Leu	missense	Exon 25 of 32	ENSP00000595449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		8.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Uncertain	0.32
Sift	Benign	0.13	T
Sift4G	Uncertain	0.0060	D
Varity_R		0.56
gMVP		0.54
Mutation Taster		=45/55	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-6637482;