rs2072374

Variant names:

• chr12-6528679-T-A
• rs2072374
• NM_014865.4:c.3300T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6528679-T-A
• chr12-6528679-T-C
• chr12-6528679-T-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_014865.4(NCAPD2):​c.3300T>A​(p.Arg1100Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R1100R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCAPD2 NM_014865.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00005526
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.690
• Publications: 28 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=0.69 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD2	NM_014865.4	c.3300T>A	p.Arg1100Arg	splice_region_variant, synonymous_variant	Exon 26 of 32	ENST00000315579.10	NP_055680.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD2	ENST00000315579.10	c.3300T>A	p.Arg1100Arg	splice_region_variant, synonymous_variant	Exon 26 of 32	1	NM_014865.4	ENSP00000325017.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455508 Hom.: 0 Cov.: 56 AF XY: 0.00 AC XY: 0 AN XY: 722592

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.00 AC: 0 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106736

Other (OTH) AF: 0.00 AC: 0 AN: 60090

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.018
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: rs2072374; hg19: chr12-6637845;