chr12-6526401-A-T

Variant names:

• chr12-6526401-A-T
• rs7311174
• NM_014865.4:c.2566+30A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014865.4(NCAPD2):​c.2566+30A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 1,613,920 control chromosomes in the GnomAD database, including 431,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47682 hom., cov: 30)
  • Exomes 𝑓: 0.72 (384125 hom.)
• Consequence: NCAPD2 NM_014865.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.942
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-6526401-A-T is Benign according to our data. Variant chr12-6526401-A-T is described in ClinVar as Benign. ClinVar VariationId is 1321845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAPD2	NM_014865.4	c.2566+30A>T		intron_variant	Intron 20 of 31	ENST00000315579.10	NP_055680.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAPD2	ENST00000315579.10	c.2566+30A>T		intron_variant	Intron 20 of 31	1	NM_014865.4	ENSP00000325017.5

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119279 AN: 151940 Hom.: 47627 Cov.: 30

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.755

GnomAD2 exomes AF: 0.746 AC: 187588 AN: 251462 AF XY: 0.735

Gnomad AFR exome AF: 0.950

Gnomad AMR exome AF: 0.862

Gnomad ASJ exome AF: 0.704

Gnomad EAS exome AF: 0.684

Gnomad FIN exome AF: 0.749

Gnomad NFE exome AF: 0.710

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.723 AC: 1057524 AN: 1461860 Hom.: 384125 Cov.: 64 AF XY: 0.721 AC XY: 524342 AN XY: 727230

African (AFR) AF: 0.955 AC: 31976 AN: 33480

American (AMR) AF: 0.857 AC: 38333 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 18506 AN: 26136

East Asian (EAS) AF: 0.676 AC: 26852 AN: 39700

South Asian (SAS) AF: 0.683 AC: 58898 AN: 86256

European-Finnish (FIN) AF: 0.750 AC: 40074 AN: 53418

Middle Eastern (MID) AF: 0.693 AC: 4000 AN: 5768

European-Non Finnish (NFE) AF: 0.715 AC: 794818 AN: 1111982

Other (OTH) AF: 0.730 AC: 44067 AN: 60396

GnomAD4 genome AF: 0.785 AC: 119396 AN: 152060 Hom.: 47682 Cov.: 30 AF XY: 0.784 AC XY: 58296 AN XY: 74310

African (AFR) AF: 0.944 AC: 39199 AN: 41510

American (AMR) AF: 0.797 AC: 12183 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2476 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3568 AN: 5162

South Asian (SAS) AF: 0.674 AC: 3241 AN: 4812

European-Finnish (FIN) AF: 0.750 AC: 7921 AN: 10558

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48460 AN: 67956

Other (OTH) AF: 0.755 AC: 1589 AN: 2106

Alfa AF: 0.750 Hom.: 7950

Bravo AF: 0.799

Asia WGS AF: 0.767 AC: 2667 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Microcephaly 21, primary, autosomal recessive Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.075
DANN	Benign	0.40
PhyloP100		-0.94
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: rs7311174; hg19: chr12-6635567;