rs2844455

Variant names:

• chr6-31901896-C-G
• rs2844455
• NM_181842.3:c.-80G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31901896-C-G
• chr6-31901896-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_181842.3(ZBTB12):​c.-80G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 143,828 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0052 (10 hom., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZBTB12 NM_181842.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 17 publications found

Genes affected

ZBTB12 (HGNC:19066): (zinc finger and BTB domain containing 12) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]

C2 Gene-Disease associations (from GenCC):

• complement component 2 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BS2: High Homozygotes in GnomAd4 at 10 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181842.3. 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
	ZBTB12	NM_181842.3	MANE Select	c.-80G>C		5_prime_UTR	Exon 1 of 2	NP_862825.1	Q9Y330
	C2	NM_001178063.3		c.73+757C>G		intron	N/A	NP_001171534.1	P06681-2
	C2	NM_001282457.2		c.-64+3954C>G		intron	N/A	NP_001269386.1	B4DQI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB12	ENST00000375527.3	TSL:1 MANE Select	c.-80G>C		5_prime_UTR	Exon 1 of 2	ENSP00000364677.2	Q9Y330
	C2	ENST00000695637.1		c.-360+3621C>G		intron	N/A	ENSP00000512074.1	A0A8Q3WKN5
	C2	ENST00000497706.6	TSL:5	c.-64+3954C>G		intron	N/A	ENSP00000417482.2	E9PDZ0

Frequencies

GnomAD3 genomes AF: 0.00517 AC: 743 AN: 143722 Hom.: 10 Cov.: 23

Gnomad AFR AF: 0.00679

Gnomad AMI AF: 0.00242

Gnomad AMR AF: 0.00234

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000225

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00659

Gnomad OTH AF: 0.00459

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 172 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 116

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 24

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 122

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome AF: 0.00517 AC: 743 AN: 143828 Hom.: 10 Cov.: 23 AF XY: 0.00456 AC XY: 319 AN XY: 69894

African (AFR) AF: 0.00678 AC: 270 AN: 39850

American (AMR) AF: 0.00234 AC: 34 AN: 14560

Ashkenazi Jewish (ASJ) AF: 0.000297 AC: 1 AN: 3368

East Asian (EAS) AF: 0.00 AC: 0 AN: 4438

South Asian (SAS) AF: 0.000225 AC: 1 AN: 4452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.00659 AC: 426 AN: 64604

Other (OTH) AF: 0.00454 AC: 9 AN: 1984

Alfa AF: 0.0000112 Hom.: 1588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.93
PhyloP100		-0.16
PromoterAI		-0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
Mutation Taster		=100/0	polymorphism

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: rs2844455; hg19: chr6-31869673;