19-19329619-A-G

Variant names:

• chr19-19329619-A-G
• rs1009136
• NM_015329.4:c.277-6099A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015329.4(MAU2):​c.277-6099A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,898 control chromosomes in the GnomAD database, including 26,300 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 0.57 (26300 hom., cov: 31)
• Consequence: MAU2 NM_015329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 19 publications found

Genes affected

MAU2 (HGNC:29140): (MAU2 sister chromatid cohesion factor) Enables protein N-terminus binding activity. Involved in cohesin loading and maintenance of mitotic sister chromatid cohesion. Located in chromatin and nuclear body. Part of Scc2-Scc4 cohesin loading complex. [provided by Alliance of Genome Resources, Apr 2022]

MAU2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAU2	NM_015329.4	c.277-6099A>G		intron_variant	Intron 1 of 18	ENST00000262815.13	NP_056144.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAU2	ENST00000262815.13	c.277-6099A>G		intron_variant	Intron 1 of 18	1	NM_015329.4	ENSP00000262815.9
MAU2	ENST00000609122.5	c.151-7551A>G		intron_variant	Intron 1 of 5	4		ENSP00000477034.1
MAU2	ENST00000586189.7	n.380-6099A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86691 AN: 151780 Hom.: 26307 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.571 AC: 86684 AN: 151898 Hom.: 26300 Cov.: 31 AF XY: 0.574 AC XY: 42636 AN XY: 74234

African (AFR) AF: 0.359 AC: 14882 AN: 41406

American (AMR) AF: 0.580 AC: 8840 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2301 AN: 3468

East Asian (EAS) AF: 0.681 AC: 3507 AN: 5148

South Asian (SAS) AF: 0.520 AC: 2504 AN: 4814

European-Finnish (FIN) AF: 0.761 AC: 8033 AN: 10560

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44746 AN: 67954

Other (OTH) AF: 0.573 AC: 1208 AN: 2110

Alfa AF: 0.630 Hom.: 47407

Bravo AF: 0.550

Asia WGS AF: 0.554 AC: 1928 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.72
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: rs1009136; hg19: chr19-19440428;