rs740850

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-6528950-C-T
• chr12-6528950-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014865.4(NCAPD2):​c.3483C>T​(p.Asn1161Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,344 control chromosomes in the GnomAD database, including 65,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9648 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55448 hom.)
• Consequence: NCAPD2 NM_014865.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 12-6528950-C-T is Benign according to our data. Variant chr12-6528950-C-T is described in ClinVar as Benign. ClinVar VariationId is 1321847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 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.3483C>T	p.Asn1161Asn	synonymous	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>T	p.Asn1161Asn	synonymous	Exon 27 of 32	ENSP00000325017.5	Q15021
	NCAPD2	ENST00000925386.1		c.3606C>T	p.Asn1202Asn	synonymous	Exon 28 of 33	ENSP00000595445.1
	NCAPD2	ENST00000925390.1		c.3522C>T	p.Asn1174Asn	synonymous	Exon 27 of 32	ENSP00000595449.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51373 AN: 151930 Hom.: 9633 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.370

GnomAD2 exomes AF: 0.303 AC: 76109 AN: 251430 AF XY: 0.295

Gnomad AFR exome AF: 0.509

Gnomad AMR exome AF: 0.411

Gnomad ASJ exome AF: 0.413

Gnomad EAS exome AF: 0.226

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.269 AC: 392959 AN: 1461296 Hom.: 55448 Cov.: 39 AF XY: 0.268 AC XY: 195083 AN XY: 726996

African (AFR) AF: 0.521 AC: 17443 AN: 33470

American (AMR) AF: 0.406 AC: 18176 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 10954 AN: 26134

East Asian (EAS) AF: 0.213 AC: 8468 AN: 39700

South Asian (SAS) AF: 0.253 AC: 21834 AN: 86248

European-Finnish (FIN) AF: 0.238 AC: 12688 AN: 53420

Middle Eastern (MID) AF: 0.398 AC: 2285 AN: 5742

European-Non Finnish (NFE) AF: 0.255 AC: 283338 AN: 1111482

Other (OTH) AF: 0.294 AC: 17773 AN: 60378

GnomAD4 genome AF: 0.338 AC: 51425 AN: 152048 Hom.: 9648 Cov.: 32 AF XY: 0.336 AC XY: 24980 AN XY: 74324

African (AFR) AF: 0.501 AC: 20760 AN: 41450

American (AMR) AF: 0.354 AC: 5416 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1155 AN: 5160

South Asian (SAS) AF: 0.253 AC: 1220 AN: 4820

European-Finnish (FIN) AF: 0.238 AC: 2517 AN: 10584

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.262 AC: 17792 AN: 67970

Other (OTH) AF: 0.366 AC: 772 AN: 2108

Alfa AF: 0.312 Hom.: 6403

Bravo AF: 0.358

Asia WGS AF: 0.279 AC: 973 AN: 3478

EpiCase AF: 0.290

EpiControl AF: 0.287

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	-0.43
CADD	Benign	5.9
DANN	Benign	0.85
PhyloP100		-1.2
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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; COSMIC: COSV57520876; COSMIC: COSV57520876;