chr19-36055035-A-G

Variant names:

• chr19-36055035-A-G
• rs1970273180
• NM_001083961.2:c.64A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001083961.2(WDR62):​c.64A>G​(p.Met22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000968 in 1,446,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M22L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: WDR62 NM_001083961.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 0 publications found

Genes affected

WDR62 (HGNC:24502): (WD repeat domain 62) This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

WDR62 Gene-Disease associations (from GenCC):

• microcephaly 2, primary, autosomal recessive, with or without cortical malformations

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P, ClinGen
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06311631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.64A>G	p.Met22Val	missense_variant	Exon 1 of 32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.64A>G	p.Met22Val	missense_variant	Exon 1 of 32	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000968 AC: 14 AN: 1446086 Hom.: 0 Cov.: 31 AF XY: 0.00000974 AC XY: 7 AN XY: 718448

African (AFR) AF: 0.00 AC: 0 AN: 33278

American (AMR) AF: 0.00 AC: 0 AN: 42900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25836

East Asian (EAS) AF: 0.00 AC: 0 AN: 38932

South Asian (SAS) AF: 0.00 AC: 0 AN: 84840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000127 AC: 14 AN: 1105672

Other (OTH) AF: 0.00 AC: 0 AN: 59722

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.0070	.;T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.063	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	M;M;.
PhyloP100		-0.18
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.23
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.16	T;T;D
Polyphen		0.0010	B;B;.
Vest4		0.18
MutPred		0.20		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;
MVP		0.34
MPC		0.23
ClinPred		0.039	T
GERP RS		0.31
PromoterAI		-0.097	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.37
Mutation Taster		=94/6	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: rs1970273180; hg19: chr19-36545937;