chr12-6529922-A-G

Variant names:

• chr12-6529922-A-G
• rs1043262
• NM_014865.4:c.3801A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014865.4(NCAPD2):​c.3801A>G​(p.Val1267Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,613,992 control chromosomes in the GnomAD database, including 428,983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45947 hom., cov: 34)
  • Exomes 𝑓: 0.72 (383036 hom.)
• Consequence: NCAPD2 NM_014865.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.700
• Publications: 26 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-6529922-A-G is Benign according to our data. Variant chr12-6529922-A-G is described in ClinVar as Benign. ClinVar VariationId is 1321849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

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.3801A>G	p.Val1267Val	synonymous	Exon 29 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.3801A>G	p.Val1267Val	synonymous	Exon 29 of 32	ENSP00000325017.5	Q15021
	NCAPD2	ENST00000925386.1		c.3924A>G	p.Val1308Val	synonymous	Exon 30 of 33	ENSP00000595445.1
	NCAPD2	ENST00000925390.1		c.3840A>G	p.Val1280Val	synonymous	Exon 29 of 32	ENSP00000595449.1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117493 AN: 152098 Hom.: 45896 Cov.: 34

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.749

GnomAD2 exomes AF: 0.744 AC: 186921 AN: 251378 AF XY: 0.733

Gnomad AFR exome AF: 0.901

Gnomad AMR exome AF: 0.860

Gnomad ASJ exome AF: 0.703

Gnomad EAS exome AF: 0.693

Gnomad FIN exome AF: 0.753

Gnomad NFE exome AF: 0.711

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.723 AC: 1056491 AN: 1461776 Hom.: 383036 Cov.: 65 AF XY: 0.720 AC XY: 523942 AN XY: 727202

African (AFR) AF: 0.907 AC: 30360 AN: 33478

American (AMR) AF: 0.854 AC: 38208 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 18488 AN: 26126

East Asian (EAS) AF: 0.686 AC: 27217 AN: 39698

South Asian (SAS) AF: 0.683 AC: 58884 AN: 86246

European-Finnish (FIN) AF: 0.754 AC: 40288 AN: 53416

Middle Eastern (MID) AF: 0.691 AC: 3986 AN: 5768

European-Non Finnish (NFE) AF: 0.715 AC: 795136 AN: 1111942

Other (OTH) AF: 0.727 AC: 43924 AN: 60382

GnomAD4 genome AF: 0.773 AC: 117606 AN: 152216 Hom.: 45947 Cov.: 34 AF XY: 0.772 AC XY: 57471 AN XY: 74410

African (AFR) AF: 0.898 AC: 37341 AN: 41564

American (AMR) AF: 0.791 AC: 12096 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2474 AN: 3472

East Asian (EAS) AF: 0.697 AC: 3594 AN: 5160

South Asian (SAS) AF: 0.674 AC: 3247 AN: 4820

European-Finnish (FIN) AF: 0.756 AC: 8000 AN: 10586

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48515 AN: 67996

Other (OTH) AF: 0.749 AC: 1581 AN: 2112

Alfa AF: 0.729 Hom.: 19541

Bravo AF: 0.784

Asia WGS AF: 0.766 AC: 2665 AN: 3478

EpiCase AF: 0.705

EpiControl AF: 0.691

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Microcephaly 21, primary, autosomal recessive (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

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: rs1043262; hg19: chr12-6639088; COSMIC: COSV57522340; COSMIC: COSV57522340;